Methods for detecting mRNA and/or protein levels of gene in a biological sample

ABSTRACT

A method to measure enhancement in the quality of life of an animal fed a super senior pet food composition comprising quantitating the gene expression levels of one or more genes in said animal and comparing said levels in the animal to levels in the animal prior to administration of said super senior pet food composition. A method to enhance the quality of life of an animal by modulating the expression level of one or more genes in said animal in order to mimic the pattern of expression seen in vivo after administration of a super senior pet food composition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of application Ser. No.12/176,331, filed on Jul. 18, 2008, now U.S. Pat. No. 8,252,742, issuedAug. 28, 2012, which is a continuation-in-part of U.S. patentapplication Ser. No. 11/813,276, filed Mar. 28, 2008, now U.S. Pat. No.8,148,325, issued Apr. 3, 2012, which is a US national stage entry under35 U.S.C. §371 of International Application No. PCT US 2005/047461 filedDec. 30, 2005, publication No. WO 2006/074089, which claims priority toU.S. Provisional Application Ser. No. 60/640,890, filed Dec. 30, 2004,each of which is incorporated by reference in its entirety for allpurposes.

FIELD OF THE INVENTION

The present invention relates generally to methods for enhancing thequality of life of an animal and particularly to using food compositionscontaining omega-3 polyunsaturated fatty acids for enhancing the qualityof life of a senior or super senior animal.

BACKGROUND OF THE INVENTION

Companion animals such as dogs and cats frequently require differingdiets depending on their life stage (age), size, body composition, andbreed. Both dog and cat nutrient requirements can be separated intothree different life-stages, based on age: growing dogs (or cats), adultdogs (or cats), and senior dogs (or cats). The latter category, seniordogs (or cats), can be further separated into two stages, which includesenior (or mature adult) and super senior (or geriatric). Dogs arefurther separated into different categories for regular breed dogsversus large-breed dogs.

Essential fatty acids, consisting of omega-3 and omega-6 polyunsaturatedfatty acids, are critical nutrients for the health of an animal. Thesenutrients, however, either cannot be made by animals or cannot be madein sufficient amounts to elicit benefits and therefore must be consumedin an animal's diet. See, e.g., Hornstra, G., et al., “Essential fattyacids in pregnancy and early human development”, Eur. J. Obs. & Gyn. andReprod. Biology, 61:57-62 (1995). It has previously been postulated thatDocosahexaenoic Acid (“DHA”), an omega-3 polyunsaturated fatty acid, iseffective in increasing the maze-learning ability and brain functions inaged mice. See, Lim, S.-Y., “Intakes of dietary docosahexaenoic acidethyl ester and egg phosphatidylcholine improve maze-learning ability inyoung and old mice”, J. Nutr., 130:1629-1632 (2000).

Rogers discusses the theory of the potential use of antioxidants to slowthe deterioration of cognitive function, particularly in the elderly.See Rogers, P., “A healthy body, a healthy mind: long-term impact ofdiet on mood and cognitive function”, Proceedings of the NutritionSociety, 60:135-143 (2001).

Despite the studies and developments relating to improving cognitiveabilities, there continues to be a need for methods for enhancing thequality of life of senior animals, as measured by, e.g., enhancedalertness, improved vitality, cartilage protection, maintenance ofmuscle mass, enhanced digestibility, and improved skin and pelagequality in senior and super senior animals. As previously reported, thesuper senior pet food composition described herein may be administeredto achieve this result. Additionally, we now report herein oursurprising discovery that the enhanced quality of life of senior andsuper senior animals achieved by the administration of the pet foodcompositions disclosed herein is reflected at the genomic level.Specifically, as described in detail in the Examples below, gene chipdata indicate that the expression of genes that encode proteinsassociated with several biological pathways such as blood clotting andplatelet activation and aggregation, bone and muscle integrity,inflammatory responses, cartilage degradation and pain response, DNAdamage and repair pathways, neural function, glycogen synthesis anddegradation, glycolysis, gluconeogenesis, the pentose phosphate pathwayand electron transport are modified, i.e., in general, the majority arebeneficially altered through administration to the animal of the supersenior pet food compositions described herein.

SUMMARY OF THE INVENTION

The invention provides methods for improving the quality of life ofsenior and super senior animals by feeding the animal a compositioncomprising at least about 9% by weight protein, at least about 5% byweight fat, and at least about 0.05% by weight of at least one omega-3polyunsaturated fatty acid.

In one embodiment, the method comprises feeding the animal an amount ofa composition effective to enhance the animal's quality of life, whereinenhanced quality of life is evidenced by improvement in one or morecharacteristics selected from the group consisting of alertness,vitality, cartilage protection, muscle mass maintenance, digestibility,and skin and pelage quality.

In another embodiment, the method comprises feeding the animal acomposition comprising at least one omega-3 polyunsaturated fatty acidselected from the group consisting of docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”). In an additional embodiment, the methodcomprises feeding the animal a composition further comprising at leastone antioxidant and at least one nutrient selected from the groupconsisting of choline, manganese, methionine, cysteine, L-carnitine,lysine, and mixtures thereof.

In one embodiment, the method comprises feeding the animal an amount ofa composition effective to improve or enhance the animal's quality oflife, wherein enhanced quality of life is evidenced by improvement inone or more biological pathways selected from the group consisting ofblood clotting and platelet activation and aggregation, bone and muscleintegrity, inflammatory responses, cartilage degradation and painresponse, DNA damage and repair pathways, neural function, glycogensynthesis and degradation, glycolysis, gluconeogenesis, the pentosephosphate pathway and electron transport.

In another embodiment, the method comprises feeding the animal an amountof a composition effective to enhance the animal's quality of life,wherein enhanced quality of life is evidenced by a change in expressionof one or more genes which encode proteins associated with or related tobiological pathways selected from the group consisting of blood clottingand platelet activation and aggregation, bone and muscle integrity,inflammatory responses, cartilage degradation and pain response, DNAdamage and repair pathways, neural function, glycogen synthesis anddegradation, glycolysis, gluconeogenesis, the pentose phosphate pathwayand electron transport.

In yet another embodiment, the invention relates to a method to treat ananimal suffering from a disorder or disease associated with or relatedto a biological pathway selected from the group consisting of bloodclotting and platelet activation and aggregation, bone and muscleintegrity, inflammatory responses, cartilage degradation and painresponse, DNA damage and repair pathways, neural function, glycogensynthesis and degradation, glycolysis, gluconeogenesis, the pentosephosphate pathway and electron transport comprising administering tosaid animal a composition disclosed herein. In one embodiment, saidcomposition comprises at least about 9% by weight protein, at leastabout 5% by weight fat, and at least about 0.05% by weight of at leastone omega-3 polyunsaturated fatty acid. In a further embodiment saidcomposition comprises at least one omega-3 polyunsaturated fatty acidselected from the group consisting of docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”). In yet an additional embodiment, thecomposition further comprises at least one antioxidant and at least onenutrient selected from the group consisting of choline, manganese,methionine, cysteine, L-carnitine, lysine, and mixtures thereof.

In another embodiment, the invention relates to methods of measuring orcharacterizing the enhancement in the quality of life of an animal,particularly a senior or super senior animal, fed a compositiondescribed herein by quantitating the gene expression levels of one ormore genes selected from a group consisting of those disclosed in Tables5-14 in said animal and comparing said levels in the animal to levels inthe animal prior to administration of the feed composition.

In a further embodiment, the invention relates to methods to enhance thequality of life of an animal by modulating the expression level of oneor more genes listed on Tables 5-14 (i.e., up or down regulation asindicated therein) in an animal in order to mimic the pattern ofexpression seen in vivo after administration of the pet foodcompositions of the present invention. It is also contemplated hereinthat modulating the expression levels of these genes may havetherapeutic value with regard to the treatment of diseases or disordersassociated with the various biological pathways.

The invention also relates to methods to identify an animal that mightbenefit from feeding a composition as disclosed herein comprisingmeasuring the gene expression levels of any one or more genes listed inTables 5-14 in said animal and comparing said levels to the geneexpression levels seen in Tables 5-14 wherein an animal with levelsdifferent than those seen in Tables 5-14 would be identified aspotentially benefiting from feeding a composition of the presentinvention.

In yet another aspect of the present invention there are provided assaymethods and kits comprising the components necessary to detectexpression of polynucleotides encoding the genes disclosed herein, orlevels of encoded protein, or fragments thereof, in body tissue samplesderived from an animal, such kits comprising, e.g., antibodies that bindto said polypeptides, or to fragments thereof, or oligonucleotide probesthat hybridize with said polynucleotides. In a preferred embodiment,such kits also comprise instructions detailing the procedures by whichthe kit components are to be used.

Other and further objects, features, and advantages of the presentinvention will be readily apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE INVENTION Definitions

It is contemplated that the invention described herein is not limited tothe particular methodology, protocols, and reagents described as thesemay vary. It is also to be understood that the terminology used hereinis for the purpose of describing particular embodiments only, and is notintended to limit the scope of the present invention in any way.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methods,devices and materials are now described. All publications mentionedherein are incorporated by reference for the purpose of describing anddisclosing the materials and methodologies that are reported in thepublication which might be used in connection with the invention.

In practicing the present invention, many conventional techniques inmolecular biology may be used. These techniques are well known and areexplained in, for example, Current Protocols in Molecular Biology,Volumes I, II, and III, 1997 (F. M. Ausubel ed.); Sambrook et al., 1989,Molecular Cloning: A Laboratory Manual, Second Edition, Cold SpringHarbor Laboratory Press, Cold Spring Harbor, N.Y.; DNA Cloning: APractical Approach, Volumes I and II, 1985 (D. N. Glover ed.);Oligonucleotide Synthesis, 1984 (M. L. Gait ed.); Nucleic AcidHybridization, 1985, (Hames and Higgins); Transcription and Translation,1984 (Hames and Higgins eds.); Animal Cell Culture, 1986 (R. I. Freshneyed.); Immobilized Cells and Enzymes, 1986 (IRL Press); Perbal, 1984, APractical Guide to Molecular Cloning; the series, Methods in Enzymology(Academic Press, Inc.); Gene Transfer Vectors for Mammalian Cells, 1987(J. H. Miller and M. P. Calos eds., Cold Spring Harbor Laboratory); andMethods in Enzymology Vol. 154 and Vol. 155 (Wu and Grossman, and Wu,eds., respectively).

As used herein and in the appended claims, the singular forms “a”, “an”,and “the” include plural reference unless the context clearly dictatesotherwise.

The terms “senior” or “mature adult” refers to the life-stage of ananimal. For small or regular breed canines, the “senior” life stage isfrom about 7 to about 10 years of age. For felines, the “senior” lifestage is from about 7 to about 12 years of age. For large breed canines,over 5 years of age represents “super senior” as described below.

The terms “super senior” or “geriatric” refers to a specific life-stageof an animal. For small or regular breed canines, the super senior stageis any age greater than 10 years of age. For large breed canines, thesuper senior stage is any age greater than 5 years of age. For felines,the super senior stage is any age greater than 12 years of age.

The term “large breed” canine means a canine that weighs more than 55pounds when an adult.

The term “regular breed” canine means a canine that weighs less than 55pounds when an adult.

The term “small breed” canine means a canine that weighs less than 20pounds when an adult.

The term “super senior pet food composition” refers to any and all ofthe pet food compositions disclosed herein.

The term “carbohydrate” as used herein includes polysaccharides (e.g.,starches and dextrins) and sugars (e.g. sucrose, lactose, maltose,glucose, and fructose) that are metabolized for energy when hydrolyzed.Examples of carbohydrates suitable for inclusion in the compositionsdisclosed herein include, but are not limited to, corn, grain sorghum,wheat, barley, and rice.

The term “antioxidant” means a substance that is capable of reactingwith free radicals and neutralizing them. Illustrative examples of suchsubstances include beta-carotene, selenium, coenzyme Q10 (ubiquinone),luetin, tocotrienols, soy isoflavones, S-adenosylmethionine,glutathione, taurine, N-acetylcysteine, vitamin E, vitamin C, lipoicacid and L-carnitine. Examples of foods containing useful levels of oneor more antioxidants include but are not limited to ginkgo biloba, greentea, broccoli, citrus pulp, grape pomace, tomato pomace, carrot spinach,and a wide variety of fruit meals and vegetable meals. It will beunderstood by one of skill in the art that while units of antioxidantsmay be provided herein as “ppm”, appropriate amounts of antioxidants mayalso be provided as “IU/kg” where appropriate and customary for a givenantioxidant such as, e.g., Vitamin E

The terms “beneficial change” in gene expression, or gene expression maybe “beneficially altered” and like terms refer to a modification in geneexpression (e.g., up or down regulation of mRNA levels) such that levelsof proteins encoded by the genes may be correspondingly modified suchthat an associated biological pathway may be more likely to functionnormally and with less tendency to reflect pathological changes in thepathway that, e.g., may be typical of a super senior animal. Generally,beneficial changes in gene expression relate to improved health and/orreduced propensity for disease in an animal. As used herein, measuringdifferences in gene expression “levels” and like terms refer to, e.g.,characterizing whether expression of a gene is up or down regulated inan animal compared to a control level.

As used herein, “improving” or “enhancing” the quality of life of ananimal refers to as an improvement or enhancement in one or morecharacteristics selected from a group consisting of alertness, vitality,protection of cartilage, maintenance of muscle mass, digestibility, andskin and pelage quality. Additionally, improvement/enhancement in bloodclotting and platelet activation and aggregation, bone and muscleintegrity, inflammatory responses, cartilage degradation and painresponse, DNA damage and repair pathways, neural function, glycogensynthesis and degradation, glycolysis, gluconeogenesis, the pentosephosphate pathway and electron transport are also contemplated.

An “improvement” or an “enhancement” in a characteristic or biologicalpathway refers to a modification in said characteristic or biologicalpathway such that there is a tendency for the characteristic or pathwayto appear and/or function normally and with less tendency to reflectpathological changes in the characteristic or pathway that, e.g., may betypical of a super senior animal.

As used herein, methods to “treat” an animal suffering from a disease ordisorder is also meant to encompass methods to prevent and/or toameliorate the disease or disorder as well.

THE INVENTION

The present invention provides methods for improving or enhancing thequality of life of a senior or super senior animal. The methods comprisefeeding the animal a composition comprising at least about 9% by weightprotein, at least about 5% by weight fat, and at least about 0.05% byweight omega-3 polyunsaturated fatty acid. The methods are useful forenhancing alertness, improving vitality, protecting cartilage,maintaining muscle mass, enhancing digestibility, and improving skin andpelage quality in a senior or super senior animal. The methods are alsouseful for improving in an animal one or more biological pathwaysselected from the group consisting of blood clotting and plateletactivation and aggregation, bone and muscle integrity, inflammatoryresponses, cartilage degradation and pain response, DNA damage andrepair pathways, neural function, glycogen synthesis and degradation,glycolysis, gluconeogenesis, the pentose phosphate pathway and theelectron transport pathway, such improvements also being reflected inoverall beneficial changes at the genomic level. Methods for treatinganimals suffering from disorders or diseases associated with or relatedto these biological pathways comprising administering the compositionsof the present invention are also contemplated herein.

Without being bound by theory, the benefits of the invention may be theresult of physiological effects from the addition of omega-3polyunsaturated fatty acids to a senior or super senior animal's diet.Similarly, the antioxidants, choline, and other nutrients may play arole in enhancing a senior or super senior animal's quality of life.

Although the methods of the present invention may improve an animal'squality of life by enhancing all of the above described characteristicsor improving all of the described biological pathways, it is notnecessary to demonstrate substantial improvements in each of thecharacteristics or pathways to achieve the “enhanced quality of life” asdefined herein.

When the compositions are administered to a senior or super senioranimal, the animal experiences an enhanced quality of life, e.g.,exhibits or experiences one or more of enhanced alertness, improvedvitality, protected cartilage, maintained muscle mass, enhanceddigestibility, improved skin and pelage quality, as well as improvementsin e.g., blood clotting and platelet activation and aggregation, boneand muscle integrity, inflammatory responses, cartilage degradation andpain response, DNA damage and repair pathways, neural function, glycogensynthesis and degradation, glycolysis, gluconeogenesis, the pentosephosphate pathway and the electron transport pathway as indicated byoverall beneficial changes at the genomic level. Methods for determiningthese measurements of quality of life are known to skilled artisans. Forexample, alertness can be measured by various means, including ananalysis of metabolism and antioxidant markers, as well as throughclinical studies with follow-up questions to participating pet owners.Potential metabolism markers may include ghrelin, GLP-1, thyroidhormone, and/or growth hormone. Potential markers of antioxidant statusmay include serum vitamin E, ORAC, glutathione peroxidase, alkanels,and/or cell damage indicators. Further, vitality can be measured byvarious means, including an analysis of metabolism and antioxidantmarkers, as well as through clinical studies with follow-up questions toparticipating pet owners. Similarly, cartilage protection can bemeasured by various means, including an analysis of arthritisbiomarkers. Potential arthritis biomarkers may include type II collagensynthesis, matrix metalloproteinase, osteocalcin, alkaline phosphataseactivity, COMP, and fragments of cartilage damage. Muscle massmaintenance can be measured by various means, including an analysis ofbody composition and digestibility can be measured by various means,including clinical studies with follow-up questions to participating petowners and animal feeding to determine the percentage of nutrientsdigested. Skin and pelage quality can be measured by various means,including clinical studies with follow-up questions to participating petowners. Additionally, as discussed above, improvements in quality oflife is also reflected at the genomic level, as evidenced by gene chipdata which indicate beneficial changes on the expression of a majorityof genes associated with various important biological pathways includingblood clotting and platelet activation and aggregation, bone and muscleintegrity, inflammatory responses, cartilage degradation and protectionand pain response, DNA damage and repair pathways, neural function,glycogen synthesis and degradation, glycolysis, gluconeogenesis, thepentose phosphate pathway and the electron transport pathway. Theidentities of these genes are provided in the Examples below.

The methods of the invention are useful for enhancing the quality oflife of humans and animals, including primates (e.g., monkeys,chimpanzees, etc.), companion animals (e.g., dogs, cats, horses, etc.),farm animals (e.g., goats, sheep, swine, cattle, etc.), laboratoryanimals (e.g., mice, rats, etc.), birds (e.g., domestic birds such ascanaries, parrots, etc. and commercial birds such as chickens, ducks,turkeys, etc.), rodents (e.g., hamsters, guinea pigs, gerbils, rabbits,hedgehogs, ferrets, chinchillas, etc.), and wild, exotic, and zooanimals (e.g., wolves, bears, deer, etc.). In various embodiments, theanimal is a cat, a dog, or a horse.

The compositions of the present invention are designed to enhancedigestibility and improve chewability. Canine and feline foods aretypically formulated based on life stage (age), size, body composition,and breed. Thus, some embodiments of the present invention includecompositions that are formulated to address specific nutritionaldifferences between regular or small breed dogs, large breed dogs, andcats.

The invention provides methods utilizing a variety of compositionscontaining at least one omega-3 polyunsaturated fatty acid. Thecompositions include foods, supplements, treats, and toys (typicallychewable and consumable toys). The methods also provide the compositionsto the designated animals over a period of time that is long enough toeffectuate the improved quality of life. In one embodiment, the methodprovides the animal with a composition for at least thirty days.

The compositions for use in the methods of the present inventiongenerally have an omega-3 polyunsaturated fatty acid content of at leastabout 0.02% (or from about 0.05% to about 10%, or from about 0.1% toabout 6%) by weight on a dry matter basis. In some embodiments, theomega-3 polyunsaturated fatty acid is DHA. In other embodiments, theomega-3 polyunsaturated fatty acid is EPA. In still other embodiments,the omega-3 polyunsaturated fatty acid comprises a mixture of DHA andEPA.

In some embodiments, the composition containing omega-3 polyunsaturatedfatty acid is a food. Although both liquid and solid foods are provided,solid foods are typically preferred. Foods include both dry foods andwet foods. Some of the non-polyunsaturated fatty acid components of thefood, and their preferred proportions, include those listed in Table 1.

TABLE 1 Proportion of the composition (% of dry weight of Componentcomposition or parts per million) Protein from about 9% to about 55%, orfrom about 18% to about 30%, or from about 33% to about 55% or fromabout 18% to about 20% or from about 33% to about 36% Fat from about 7%to about 35%, or from about 18% to about 35%, or from about 7% to about24%, or from about 14% to about 24%, or from about 14% to about 16% orfrom about 18% to about 24% Antioxidant from about 0 ppm to about 7500ppm, or from about 0.05 ppm to about 3600 ppm, or from about 250 toabout 3600, or from about 250 ppm to about 1650 ppm, or from about 5 ppmto about 225 ppm, or from about 0.05 ppm to about 2.4 ppm

In one embodiment, the methods of this invention comprise feeding asuper senior animal a composition in an amount effective to enhance theanimal's quality of life. Such compositions generally comprise:

-   -   (a) 0.02% (or from about 0.05% to about 10%, or from about 0.1%        to about 6%) at least one omega-3 polyunsaturated fatty acid,        and    -   (b) at least one of the following:        -   (i) from about 10% to about 55% (or from about 18% to about            30%, or from about 33% to about 55% or from about 18% to            about 20% or from about 33% to about 36%) protein,        -   (ii) from about 7% to about 35% (or from about 18% to about            35%, or from about 7% to about 24%, or from about 14% to            about 24%, or from about 14% to about 16% or from about 18%            to about 24%) fat, and        -   (iii) at least about 0.05 (or from about 0.05 ppm or IU/kg            to about 7500 ppm or IU/kg, or from about 250 ppm or IU/kg            to about 3600 ppm or IU/kg, or from about 250 ppm or IU/kg            to about 1650 ppm or IU/kg, or from about 5 ppm or IU/kg to            about 225 ppm or IU/kg, or from about 0.05 ppm or IU/kg to            about 2.4 ppm or IU/kg) antioxidant.

In another embodiment, the methods of this invention comprise feeding asuper senior regular or small breed canine a composition in an amounteffective to enhance the canine's quality of life. The compositiongenerally comprises:

-   -   (a) at least one of the following:        -   (i) at least about 0.02% (or from about 0.02% to about 0.3%,            or from about 0.05% to about 0.3%, or from about 0.05% to            about 0.2%) DHA, and        -   (ii) at least about 0.1% (or from about 0.1% to about 0.5%,            or from about 0.2% to about 0.5%, or from about 0.2% to            about 0.3%) EPA,    -   (b) at least about 9% (or from about 9% to about 30%, or from        about 18% to about 30%0, or from about 18% to about 20%)        protein,    -   (c) at least about 7% (or from about 7% to about 24%, or from        about 14% to about 24%, or from about 14% to about 16%) fat, and    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1000 IU/kg) vitamin            E,        -   (iv) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 100 ppm to about 500 ppm, or from            about 100 ppm to about 301 ppm) vitamin C,        -   (v) at least about 600 ppm (or from about 600 ppm to about            2400 ppm, or from about 1260 ppm to about 2400 ppm, or from            about 1260 ppm to about 1545 ppm) taurine,        -   (vi) at least about 50 ppm (or from about 50 ppm to about            200 ppm, or from about 100 to about 160, or from about 100            to about 155) lipoic acid, and        -   (vii) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 200 ppm to about 500 ppm, or from            about 200 ppm to about 350 ppm) carnitine.

In another embodiment, the methods of this invention comprise feeding asuper senior large breed canine a composition in an amount effective toenhance the canine's quality of life. The compositions generallycomprise:

-   -   (a) at least one of the following:        -   (i) at least about 0.02% (or from about 0.02% to about 0.3%,            or from about 0.05% to about 0.3%, or from about 0.05% to            about 0.2%) DHA, and        -   (ii) at least about 0.1% (or from about 0.1% to about 0.5%,            or from about 0.2% to about 0.5%, or from about 0.2% to            about 0.3%) EPA,    -   (b) at least about 9% (or from about 9% to about 30%, or from        about 18% to about 30%0, or from about 18% to about 20%)        protein,    -   (c) at least about 7% (or from about 7% to about 24%, or from        about 14% to about 24%, or from about 14% to about 16%) fat, and    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1000 IU/kg) vitamin            E,        -   (viii) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 100 ppm to about 500 ppm, or from            about 100 ppm to about 301 ppm) vitamin C,        -   (ix) at least about 600 ppm (or from about 600 ppm to about            2400 ppm, or from about 1260 ppm to about 2400 ppm, or from            about 1260 ppm to about 1575 ppm) taurine, and        -   (x) at least about 50 ppm (or from about 50 ppm to about 200            ppm, or from about 100 to about 160, or from about 100 to            about 155) lipoic acid, and        -   (xi) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 200 ppm to about 500 ppm, or from            about 200 ppm to about 350 ppm) carnitine.

In another embodiment, the methods of this invention comprise feeding asuper senior feline a composition in an amount effective to enhance thefeline's quality of life. The compositions generally comprise:

-   -   (a) at least one of the following:        -   (i) at least about 0.05% (or from about 0.05% to about            0.30%, or from about 0.1% to about 0.30%, or from about 0.1%            to about 0.2%) DHA, and        -   (ii) at least about 0.1% (or from about 0.1% to about 0.5%,            or from about 0.2% to about 0.5%, or from about 0.2% to            about 0.3%) EPA,    -   (b) at least about 15% (or from about 15% to about 55%, or from        about 30% to about 55%, or from about 33% to about 36%) protein,    -   (c) at least about 9% (or from about 9% to about 35%, or from        about 18% to about 35%, or from about 18% to about 24%) fat, and    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1100 IU/kg) vitamin            E,        -   (xii) at least about 50 ppm (or from about 50 ppm to about            300 ppm, or from about 100 ppm to about 300 ppm, or from            about 100 ppm to about 200 ppm) vitamin C,        -   (xiii) at least about 1100 ppm (or from about 1100 ppm to            about 3500 ppm, or from about 2300 ppm to about 3500 ppm, or            from about 2300 ppm to about 2350 ppm) taurine, and        -   (xiv) at least about 200 ppm (or from about 200 to about 750            ppm, or from about 400 ppm to about 750 ppm, or from about            400 to about 525 ppm) carnitine, and        -   (xv) at least about 0.05% (or from about 0.05% to about            0.6%, or from about 0.1% to about 0.6%, or from about 0.1%            to about 0.4%) cystine.

In another embodiment, the methods of this invention comprise feeding asuper senior animal a composition in an amount effective to enhance theanimal's alertness and vitality. The composition generally comprises:

-   -   (a) 0.02% (or from about 0.05% to about 10%, or from about 0.1%        to about 6%) at least one omega-3 polyunsaturated fatty acid,        and    -   (b) at least one of the following:        -   (xvi) from about 10% to about 55% (or from about 18% to            about 30%, or from about 33% to about 55% or from about 18%            to about 20% or from about 33% to about 36%) protein,        -   (xvii) from about 7% to about 35% (or from about 18% to            about 35%, or from about 7% to about 24%, or from about 14%            to about 24%, or from about 14% to about 16% or from about            18% to about 24%) fat,        -   (xviii) at least about 0.05 (or from about 0.05 ppm to about            7500 ppm, or from about 250 to about 3600, or from about 250            ppm to about 1650 ppm, or from about 5 ppm to about 225 ppm,            or from about 0.05 ppm to about 2.4 ppm) antioxidant, and        -   (xix) at least about 1000 ppm (or from about 1000 ppm to            about 5000 ppm, from about 3300 ppm to about 5000 ppm, or            from about 2000 ppm to about 3000 ppm, or from about 3000            ppm to about 4000 ppm) choline.

In another embodiment, the methods of this invention comprise feeding asuper senior regular or small breed canine a composition in an amounteffective to enhance the canine's alertness and vitality. Thecomposition generally comprises:

-   -   (a) at least one of the following:        -   (i) at least about 0.02% (or from about 0.02% to about 0.3%,            or from about 0.05% to about 0.3%, or from about 0.05% to            about 0.2%) DHA, and (ii) at least about 0.1% (or from about            0.1% to about 0.5%, or from about 0.2% to about 0.5%, or            from about 0.2% to about 0.3%) EPA,    -   (b) at least about 9% (or from about 9% to about 30%, or from        about 18% to about 30%, or from about 18% to about 20%) protein,    -   (c) at least about 7% (or from about 7% to about 24%, or from        about 14% to about 24%, or from about 14% to about 16%) fat,    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1000 IU/kg) vitamin            E,        -   (xx) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 100 ppm to about 500 ppm, or from            about 100 ppm to about 301 ppm) vitamin C,        -   (xxi) at least about 600 ppm (or from about 600 ppm to about            2400 ppm, or from about 1260 ppm to about 2400 ppm, or from            about 1260 ppm to about 1545 ppm) taurine, and        -   (xxii) at least about 50 ppm (or from about 50 ppm to about            200 ppm, or from about 100 to about 160, or from about 100            to about 155) lipoic acid, and        -   (xxiii) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 200 ppm to about 500 ppm, or from            about 200 ppm to about 350 ppm) carnitine,    -   (e) at least about 1000 ppm (or from about 1000 ppm to about        3200 ppm, or from about 2000 ppm to about 3200 ppm, or from        about 2000 ppm to about 2500 ppm) choline,    -   (f) at least about 50 ppm (or from about 50 ppm to about 150        ppm, or from about 100 ppm to about 150 ppm, or from about 100        ppm to about 110 ppm) manganese, and    -   (g) at least about 0.4% (or from about 0.4% to about 2%, or from        about 0.9% to about 2%, or from about 0.9% to about 1.2%)        lysine, and    -   (h) at least about 0.4% to about 1.5% methionine.

In another embodiment, the methods of this invention comprise feeding asuper senior large breed canine a composition in an amount effective toenhance the canine's alertness and vitality. The composition generallycomprises:

-   -   (a) at least one of the following:        -   (i) at least about 0.02% (or from about 0.02% to about 0.3%,            or from about 0.05% to about 0.3%, or from about 0.05% to            about 0.2%) DHA, and        -   (ii) at least about 0.1% (or from about 0.1% to about 0.5%,            or from about 0.2% to about 0.5%, or from about 0.2% to            about 0.3%) EPA,    -   (b) at least about 9% (or from about 9% to about 30%, or from        about 18% to about 30%, or from about 18% to about 20%) protein,    -   (c) at least about 7% (or from about 7% to about 24%, or from        about 14% to about 24%, or from about 14% to about 16%) fat,    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1000 IU/kg) vitamin            E,        -   (xxiv) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 100 ppm to about 500 ppm, or from            about 100 ppm to about 301 ppm) vitamin C,        -   (xxv) at least about 600 ppm (or from about 600 ppm to about            2400 ppm, or from about 1260 ppm to about 2400 ppm, or from            about 1260 ppm to about 1575 ppm) taurine, and        -   (xxvi) at least about 50 ppm (or from about 50 ppm to about            200 ppm, or from about 100 to about 160, or from about 100            to about 155) lipoic acid, and        -   (xxvii) at least about 50 ppm (or from about 50 ppm to about            500 ppm, or from about 200 ppm to about 500 ppm, or from            about 200 ppm to about 350 ppm) carnitine,    -   (e) at least about 1000 ppm (or from about 1000 ppm to about        3200 ppm, or from about 2000 ppm to about 3200 ppm, or from        about 2000 ppm to about 2500 ppm) choline,    -   (f) at least about 50 ppm (or from about 50 ppm to about 150        ppm, or from about 100 ppm to about 150 ppm, or from about 100        ppm to about 110 ppm) manganese, and    -   (g) at least about 0.4% (or from about 0.4% to about 2%, or from        about 0.9% to about 2%, or from about 0.9% to about 1.2%)        lysine, and    -   (h) at least about 0.4% to about 1.5% methionine.

In another embodiment, the methods of this invention comprise feeding asuper senior feline a composition in an amount effective to enhance thefeline's alertness and vitality. The composition generally comprises:

-   -   (a) at least one of the following:        -   (i) at least about 0.05% (or from about 0.05% to about            0.30%, or from about 0.1% to about 0.30%, or from about 0.1%            to about 0.2%) DHA, and        -   (ii) at least about 0.1% (or from about 0.1% to about 0.5%,            or from about 0.2% to about 0.5%, or from about 0.2% to            about 0.3%) EPA,    -   (b) at least about 15% (or from about 15% to about 55%, or from        about 30% to about 55%, or from about 33% to about 36%) protein,    -   (c) at least about 9% (or from about 9% to about 35%, or from        about 18% to about 35%, or from about 18% to about 24%) fat,    -   (d) at least one of the following:        -   (i) at least about 250 IU/kg (or from about 250 IU/kg to            about 1500 IU/kg, or from about 500 IU/kg to about 1500            IU/kg, or from about 500 IU/kg to about 1100 IU/kg) vitamin            E,        -   (xxviii) at least about 50 ppm (or from about 50 ppm to            about 300 ppm, or from about 100 ppm to about 300 ppm, or            from about 100 ppm to about 200 ppm) vitamin C,        -   (xxix) at least about 1100 ppm (or from about 1100 ppm to            about 3500 ppm, or from about 2300 ppm to about 3500 ppm, or            from about 2300 ppm to about 2350 ppm) taurine, and        -   (xxx) at least about 200 ppm (or from about 200 to about 750            ppm, or from about 400 ppm to about 750 ppm, or from about            400 to about 525 ppm) carnitine, and        -   (xxxi) at least about 0.05% (or from about 0.05% to about            0.6%, or from about 0.1% to about 0.6%, or from about 0.1%            to about 0.4%) cystine.    -   (e) at least about 1600 ppm (or from about 1600 ppm to about        5000 ppm, or from about 3300 ppm to about 5000 ppm, or from        about 3300 ppm to about 3400 ppm) choline,    -   (f) at least about 50 ppm (or from about 50 ppm to about 150        ppm, or from about 100 ppm to about 150 ppm, or from about 100        ppm to about 110 ppm) manganese, and    -   (g) at least about 0.7% (or from about 0.7% to about 3%, or from        about 1.4% to about 3%, or from about 1.4% to about 1.7%)        lysine, and    -   (h) at least about 0.4% to about 1.5% methionine.

In another embodiment, this invention provides a method for improvingthe quality of life of a senior or super senior small or regular breedcanine. The method comprises feeding the canine a compositioncomprising:

-   -   from about 60% to about 70% by weight carbohydrate;    -   from about 15% to about 25% by weight protein selected from the        group consisting of animal protein and vegetable protein;    -   from about 5% to about 7% by weight fat selected from the group        consisting of animal fat and vegetable fat;    -   from about 2.5% to about 4% by weight of at least one omega-3        polyunsaturated fatty acids;    -   from about 1% to about 4% by weight fiber;    -   from about 1% to about 2% by weight minerals; and    -   from about 0.5 to about 1.5% by weight vitamins.

In another embodiment, this invention provides a method for improvingthe quality of life of a senior or super senior large breed canine. Themethod comprises feeding the canine a composition comprising:

-   -   from about 60% to about 70% by weight carbohydrate;    -   from about 15% to about 25% by weight protein selected from the        group consisting of animal protein and vegetable protein;    -   from about 5% to 10% by weight fat selected from the group        consisting of animal fat and vegetable fat;    -   from about 3% to about 5% by weight of at least one omega-3        polyunsaturated fatty acids;    -   from about 1% to about 4% by weight fiber;    -   from about 0.5% to about 1% by weight minerals; and    -   from about 0.75 to about 1.25% by weight vitamins.

In another embodiment, this invention provides a method for improvingthe quality of life of a senior or super senior feline. The methodcomprises feeding the feline a composition comprising:

-   -   from about 30% to about 35% by weight carbohydrate;    -   from about 35% to about 50% by weight protein selected from the        group consisting of animal protein and vegetable protein;    -   from about 12% to about 15% by weight fat selected from the        group consisting of animal fat and vegetable fat;    -   from about 1% to about 2% by weight of at least one omega-3        polyunsaturated fatty acids;    -   from about 1% to about 5% by weight fiber;    -   from about 1% to about 2% by weight minerals; and    -   from about 1% to about 2% by weight vitamins.

In a further embodiment, this invention provides a method for improvingthe quality of life of a senior or super senior animal comprisingfeeding the animal (e.g., small, regular or large breed canine orfeline, as the case may be) a composition comprising the components asindicated in Table 1A below:

TABLE 1A Chemical composition of Super Senior Foods Small/Regular LargeBreed Breed Nutrient Component Canine Canine Feline Crude Protein, %20.1 9.34 35.73 Fat, % 16.45 16.92 22.47 Calcium, % 0.71 0.73 0.94Phosphorus, % 0.61 0.68 0.77 EPA, % 0.32 0.32 0.23 DHA, % 0.22 0.22 0.32Linoleic Acid, % 3.96 4.04 5.05 Total N-3 fatty acids, % 1.3 2.24 1.14Total N-6 fatty acids, % 3.96 3.99 5.09 Taurine, ppm 1400 15.25 2100Carnitine, ppm 314 337 367 Methinoinine, % 1 1.19 1.32 Cystine, % 0.250.24 0.47 Manganese, ppm 87 100 104 Vitamin E, IU/kg 1492 1525 1292Vitamin C, ppm 127 261 141 Lipoic Acid, ppm* 101 135 *Lipoic acid basedon formulated, not analyzed values.

The compositions for use in the methods of this invention furthercomprise at least one nutrient selected from the group consisting ofmanganese, methionine, cysteine, mixtures of methionine and cysteine,L-carnitine, lysine, and arginine. Specific preferred amounts for eachcomponent in a composition will depend on a variety of factorsincluding, for example, the species of animal consuming the composition;the particular components included in the composition; the age, weight,general health, sex, and diet of the animal; the animal's consumptionrate, and the like. Thus, the component amounts may vary widely, and mayeven deviate from the proportions given herein.

The omega-3 fatty acids may be obtained from a variety of sources. Oneconvenient source is fish oils from, for example, menhaden, mackerel,herring, anchovy, and salmon. DHA and EPA are typical fatty acidspresent in such fish oils, and, together often make up a significantportion of the oil, such as from about 25% to about 38% of the oil.

When the composition is an animal food, vitamins and minerals preferablyare included in amounts required to avoid deficiency and maintainhealth. These amounts are readily available in the art. The NationalResearch Council (NRC), for example, provides recommended amounts ofsuch ingredients for farm animals. See, e.g., Nutrient Requirements ofSwine (10th Rev. Ed., Nat'l Academy Press, Wash. D.C., 197298), NutrientRequirements of Poultry (9th Rev. Ed. Nat'l Academy Press, Wash. D.C.,1994), Nutrient Requirements of Horses (Fifth Rev. Ed., Nat'l AcademyPress, Wash. D.C., 1989), Nutrient Requirements of Dogs and Cats (Nat'lAcademy Press, Wash. D.C., 2006). The American Feed Control Officials(AAFCO), for example, provides recommended amounts of such ingredientsfor dogs and cats. See American Feed Control Officials, Inc., Officialpublication, pp. 126-140 (2003). Examples of vitamins useful as foodadditives include vitamin A, B1, B2, B6, B12, C, D, E, K, H (biotin), K,folic acid, inositol, niacin, and pantothenic acid. Examples of mineralsand trace elements useful as food additives include calcium, phosphorus,sodium, potassium, magnesium, copper, zinc, chloride, and iron salts.

The methods of the present invention include compositions that mayfurther contain other additives known in the art. Preferably, suchadditives are present in amounts that do not impair the purpose andeffect provided by the invention. Examples of additives include, forexample, substances with a stabilizing effect, processing aids,substances that enhance palatability, coloring substances, andsubstances that provide nutritional benefits.

Stabilizing substances include, for example, substances that tend toincrease the shelf life of the composition. Potentially suitableexamples of such substances include, for example, preservatives,antioxidants, synergists and sequestrants, packaging gases, stabilizers,emulsifiers, thickeners, gelling agents, and humectants. Examples ofemulsifiers and/or thickening agents include, for example, gelatin,cellulose ethers, starch, starch esters, starch ethers, and modifiedstarches.

Additives for coloring, palatability (“pal enhancers”), and nutritionalpurposes include, for example, colorants (e.g., iron oxide, such as thered, yellow, or brown forms); sodium chloride, potassium citrate,potassium chloride, and other edible salts; vitamins; minerals; andflavoring. Such additives are known in the art. See, e.g., U.S. Pat. No.3,202,514. See also, U.S. Pat. No. 4,997,671. Flavorants include, forexample, dairy product flavorants (e.g., milk or cheese), meatflavorants (e.g., bacon, liver, beef, poultry, or fish), oleoresin,pinacol, and the various flavorants identified in the trade by a FEMA(Flavor Extract Manufacturers Association) number. Flavorants helpprovide additional palatability, and are known in the art. See, e.g.,U.S. Pat. No. 4,997,672. See also, U.S. Pat. No. 5,004,624. See also,U.S. Pat. No. 5,114,704. See also, U.S. Pat. No. 5,532,010. See also,U.S. Pat. No. 6,379,727. The concentration of such additives in thecomposition typically may be up to about 5% by weight. In someembodiments, the concentration of such additives (particularly wheresuch additives are primarily nutritional balancing agents, such asvitamins and minerals) is from about 0% to about 2.0% by weight. In someembodiments, the concentration of such additives (again, particularlywhere such additives are primarily nutritional balancing agents) is fromabout 0% to about 1.0% by weight.

Supplements include, for example, a feed used with another feed toimprove the nutritive balance or performance of the total. Supplementsinclude compositions that are fed undiluted as a supplement to otherfeeds, offered free choice with other parts of an animal's ration thatare separately available, or diluted and mixed with an animal's regularfeed to produce a complete feed. The AAFCO, for example, provides adiscussion relating to supplements in the American Feed ControlOfficials, Inc. Official Publication, p. 220 (2003). Supplements may bein various forms including, for example, powders, liquids, syrups,pills, encapsulated compositions, and the like.

Treats include, for example, compositions that are given to an animal toentice the animal to eat during a non-meal time. Treats for caninesinclude, for example, dog bones. Treats may be nutritional, wherein thecomposition comprises one or more nutrients, and may, for example, havea composition as described above for food. Non-nutritional treatsencompass any other treats that are non-toxic.

Toys include, for example, chewable toys. Toys for dogs include, forexample, artificial bones. There is a wide range of suitable toyscurrently marketed. See, e.g., U.S. Pat. No. 5,339,771 (and referencesdisclosed in U.S. Pat. No. 5,339,771). See also, e.g., U.S. Pat. No.5,419,283 (and references disclosed in U.S. Pat. No. 5,419,283). Theinvention provides both partially consumable toys (e.g., toys comprisingplastic components) and fully consumable toys (e.g., rawhides andvarious artificial bones). It should be further recognized that thisinvention provides toys for both human and non-human use, particularlyfor companion, farm, and zoo animal use, and particularly for dog, cat,or bird use.

A “food” is a nutritionally complete diet for the intended recipientanimal (e.g., domestic cat or domestic dog). A “nutritionally completediet” is a diet that includes sufficient nutrients for maintenance ofnormal health of a healthy animal on the diet. The methods of thisinvention utilize compositions that are not intended to be restricted byany specific listing of proteinaceous or fat ingredients or productform. The compositions can be prepared in, for example, a dry, canned,wet, or intermediate moisture form using conventional pet foodprocesses. In some embodiments, the moisture content is from about 10%to about 90% of the total weight of the composition. In otherembodiments, the moisture content is from about 65% to about 75% of thetotal weight of the composition.

In preparing a composition for use with the methods of the presentinvention, any ingredient (e.g., fish oil) generally may, for example,be incorporated into the composition during the processing of theformulation, such as during and/or after mixing of other components ofthe composition. Distribution of these components into the compositioncan be accomplished by conventional means. In one embodiment, groundanimal and poultry proteinaceous tissues are mixed with the otheringredients, including fish oils, cereal grains, other nutritionallybalancing ingredients, special-purpose additives (e.g., vitamin andmineral mixtures, inorganic salts, cellulose and beet pulp, bulkingagents, and the like); and water that is sufficient for processing isalso added. These ingredients preferably are mixed in a vessel suitablefor heating while blending the components. Heating of the mixture may beeffected using any suitable manner, such as, for example, by directsteam injection or by using a vessel fitted with a heat exchanger.Following the addition of the last ingredient, the mixture is heated toa temperature range of from about 50° F. (10° C.) to about 212° F. (100°C.). In some embodiments, the mixture is heated to a temperature rangeof from about 70° F. (21° C.) to about 140° F. (60° C.). Temperaturesoutside these ranges are generally acceptable, but may be commerciallyimpractical without use of other processing aids. When heated to theappropriate temperature, the material will typically be in the form of athick liquid. The thick liquid is filled into cans. A lid is applied,and the container is hermetically sealed. The sealed can is then placedinto conventional equipment designed to sterilize the contents. This isusually accomplished by heating to temperatures of greater than about230° F. (110° C.) for an appropriate time, which is dependent on, forexample, the temperature used and the composition.

Methods of the present invention include utilizing compositions that canbe prepared in a dry form using conventional processes. In oneembodiment, dry ingredients, including, for example, animal proteinsources, plant protein sources, grains, etc., are ground and mixedtogether. Moist or liquid ingredients, including fats, oils, animalprotein sources, water, etc., are then added to and mixed with the drymix. The mixture is then processed into kibbles or similar dry pieces.Kibble is often formed using an extrusion process in which the mixtureof dry and wet ingredients is subjected to mechanical work at a highpressure and temperature, and forced through small openings and cut offinto kibble by a rotating knife. The wet kibble is then dried andoptionally coated with one or more topical coatings which may include,for example, flavors, fats, oils, powders, and the like. Kibble also canbe made from the dough using a baking process, rather than extrusion,wherein the dough is placed into a mold before dry-heat processing.

The compositions are also designed to be easier to chew. Canine andfeline foods are typically formulated based on life stage (age), size,body composition, and breed. In the methods of this invention, someembodiments of the compositions address specific nutritional differencesbetween super senior regular or small breed dogs, large breed dogs, andcats.

All percentages expressed herein are on a weight by dry matter basisunless specifically stated otherwise.

As noted previously, this invention is directed, in part, to a methodfor enhancing the quality of life of an animal. The method comprisesfeeding a senior or super senior animal a composition in an amounteffective to enhance alertness, improve vitality, protect cartilage,maintain muscle mass, enhance digestibility, and improve skin and pelagequality. Additionally, we now report herein our surprising discoverythat the enhanced quality of life of an animal achieved byadministration of the compositions of the present invention is reflectedat the genomic level. While it may be that a change in expression of anyone gene disclosed in the tables presented below may result inbeneficial or deleterious biological effects, the data presented hereinindicate that, overall, the observed expression profiles are consistentwith the beneficial biological effects seen in vivo after administrationof the diets disclosed herein. Specifically, gene chip data indicatethat the expression of genes that encode proteins associated with orrelated to several biological pathways such as blood clotting andplatelet activation and aggregation, bone and muscle integrity,inflammatory responses, cartilage degradation and pain response, DNAdamage and repair pathways, neural function, glycogen synthesis anddegradation, glycolysis, gluconeogenesis, the pentose phosphate pathwayand electron transport are, for the most part, beneficially alteredthrough administration to the animal of compositions described herein.Thus, the invention also relates to methods of measuring orcharacterizing the enhancement in the quality of life of an animal,particularly a senior or super senior animal, fed a compositiondescribed herein by quantitating the gene expression levels of one ormore genes selected from a group consisting of those disclosed in Tables5-14 in said animal and comparing said levels in the animal to levels inthe animal prior to administration of the feed composition. Quantitationof gene expression may be carried out in numerous ways familiar to oneof skill in the art and include such techniques as RT PCR as well asgene chip assays and Northern blotting. Thus, it is contemplated hereinthat the expression levels detected may be used, for example, in methodsto measure enhancement in the quality of life of an animal as disclosedherein.

In another aspect, the present invention relates to kits which comprise:

(a) a polynucleotide of a gene disclosed herein or a fragment thereof;

(b) a nucleotide sequence complementary to that of (a);

(c) a polypeptide encoded by a gene disclosed herein, or a fragmentthereof, or

(d) an antibody to a polypeptide encoded by a gene disclosed herein, ora fragment thereof.

It will be appreciated that in any such kit, (a), (b), (c) or (d) maycomprise a substantial component. The manufacture of kits as describedherein and components thereof (e.g., antibody production) may beachieved according to conventional methods.

It is contemplated herein that modulating the expression levels of thegenes disclosed herein may have therapeutic value with regard to thetreatment of diseases or disorders associated with the variousbiological pathways. Such determination may be made on a gene by genebasis without undue experimentation, for example, by assessingexpression levels in tissues as well as in blood samples, or by assayingexpression levels in vitro in cells or cell lines relevant to particulardisease states and suitable for such experimentation. In vivo models ofdisease might also be utilized in such experimentation. The nature ofthese and other suitable additional assays would be familiar to one ofskill in the art. Thus, based on the genomic data disclosed herein, theinvention also relates to methods to enhance the quality of life of ananimal by modulating the expression level of one or more genes listed onTables 5-14 (i.e. up or down regulation as indicated therein) in ananimal in order to mimic the pattern of expression seen in vivo afteradministration of the pet food compositions of the present invention.

Modulation of gene expression levels may be achieved through the use ofknown modulators of gene expression suitable for administration in vivo,including, but not limited to, ribozymes, antisense oligonucleotides,triple helix DNA, RNA aptamers and/or double stranded RNA directed to anappropriate nucleotide sequence of a gene of interest. These inhibitorymolecules may be created using conventional techniques by one of skillin the art without undue burden or experimentation. For example,modification (e.g. inhibition) of gene expression may be obtained bydesigning antisense molecules, DNA or RNA, to the control regions of thegenes discussed herein, i.e. to promoters, enhancers, and introns. Forexample, oligonucleotides derived from the transcription initiationsite, e.g., between positions −10 and +10 from the start site may beused. Notwithstanding, all regions of the gene may be used to design anantisense molecule in order to create those which gives strongesthybridization to the mRNA and such suitable antisense oligonucleotidesmay be produced and identified by standard assay procedures familiar toone of skill in the art.

Similarly, inhibition of gene expression may be achieved using “triplehelix” base-pairing methodology. Triple helix pairing is useful becauseit causes inhibition of the ability of the double helix to opensufficiently for the binding of polymerases, transcription factors, orregulatory molecules. Recent therapeutic advances using triplex DNA havebeen described in the literature (Gee, J. E. et al. (1994) In: Huber, B.E. and B. I. Carr, Molecular and Immunologic Approaches, FuturaPublishing Co., Mt. Kisco, N.Y.). These molecules may also be designedto block translation of mRNA by preventing the transcript from bindingto ribosomes.

Ribozymes, enzymatic RNA molecules, may also be used to modulate geneexpression by catalyzing the specific cleavage of RNA. The mechanism ofribozyme action involves sequence-specific hybridization of the ribozymemolecule to complementary target RNA, followed by endonucleolyticcleavage. Examples which may be used include engineered “hammerhead” or“hairpin” motif ribozyme molecules that can be designed to specificallyand efficiently catalyze endonucleolytic cleavage of gene sequences.

Specific ribozyme cleavage sites within any potential RNA target areinitially identified by scanning the target molecule for ribozymecleavage sites which include the following sequences: GUA, GUU and GUC.Once identified, short RNA sequences of between 15 and 20ribonucleotides corresponding to the region of the target genecontaining the cleavage site may be evaluated for secondary structuralfeatures which may render the oligonucleotide inoperable. Thesuitability of candidate targets may also be evaluated by testingaccessibility to hybridization with complementary oligonucleotides usingribonuclease protection assays.

Ribozyme methods include exposing a cell to ribozymes or inducingexpression in a cell of such small RNA ribozyme molecules (Grassi andMarini, 1996, Annals of Medicine 28: 499-510; Gibson, 1996, Cancer andMetastasis Reviews 15: 287-299). Intracellular expression of hammerheadand hairpin ribozymes targeted to mRNA corresponding to at least one ofthe genes discussed herein can be utilized to inhibit protein encoded bythe gene.

Ribozymes can either be delivered directly to cells, in the form of RNAoligonucleotides incorporating ribozyme sequences, or introduced intothe cell as an expression vector encoding the desired ribozymal RNA.Ribozymes can be routinely expressed in vivo in sufficient number to becatalytically effective in cleaving mRNA, and thereby modifying mRNAabundance in a cell (Cotten et al., 1989 EMBO J. 8:3861-3866). Inparticular, a ribozyme coding DNA sequence, designed according toconventional, well known rules and synthesized, for example, by standardphosphoramidite chemistry, can be ligated into a restriction enzyme sitein the anticodon stem and loop of a gene encoding a tRNA, which can thenbe transformed into and expressed in a cell of interest by methodsroutine in the art. Preferably, an inducible promoter (e.g., aglucocorticoid or a tetracycline response element) is also introducedinto this construct so that ribozyme expression can be selectivelycontrolled. For saturating use, a highly and constituently activepromoter can be used. tDNA genes (i.e., genes encoding tRNAs) are usefulin this application because of their small size, high rate oftranscription, and ubiquitous expression in different kinds of tissues.Therefore, ribozymes can be routinely designed to cleave virtually anymRNA sequence, and a cell can be routinely transformed with DNA codingfor such ribozyme sequences such that a controllable and catalyticallyeffective amount of the ribozyme is expressed. Accordingly the abundanceof virtually any RNA species in a cell can be modified or perturbed.

Ribozyme sequences can be modified in essentially the same manner asdescribed for antisense nucleotides, e.g., the ribozyme sequence cancomprise a modified base moiety.

RNA aptamers can also be introduced into or expressed in a cell tomodify RNA abundance or activity. RNA aptamers are specific RNA ligandsfor proteins, such as for Tat and Rev RNA (Good et al., 1997, GeneTherapy 4: 45-54) that can specifically inhibit their translation.

Gene specific inhibition of gene expression may also be achieved usingconventional RNAi technologies. Numerous references describing suchtechnologies exist and include, for example, WO 99/32619; Miller et al.Cell Mol Neurobiol 25:1195-207 (2005); Lu et al. Adv Genet 54:117-42(2005).

Antisense molecules, triple helix DNA, RNA aptamers and ribozymes of thepresent invention may be prepared by any method known in the art for thesynthesis of nucleic acid molecules. These include techniques forchemically synthesizing oligonucleotides such as solid phasephosphoramidite chemical synthesis. Alternatively, RNA molecules may begenerated by in vitro and in vivo transcription of DNA sequencesencoding the genes discussed herein. Such DNA sequences may beincorporated into a wide variety of vectors with suitable RNA polymerasepromoters such as T7 or SP6 according to conventional methods.Alternatively, cDNA constructs that synthesize antisense RNAconstitutively or inducibly can be introduced into cell lines, cells, ortissues using methods familiar to one of skill in the art. Vectors maybe introduced into cells or tissues by many available means, and may beused in vivo, in vitro or ex vivo. For ex vivo therapy, vectors may beintroduced into stem cells taken from an animal and clonally propagatedfor autologous transplant back into that same animal. Delivery bytransfection and by liposome injections may be achieved using methodsthat are well known in the art.

The instant invention also includes a method to identify an animal thatmight benefit from feeding a composition as disclosed herein comprisingmeasuring the gene expression levels of any one or more genes listed inTables 5-14 in said animal and comparing said levels to the geneexpression levels seen in Tables 5-14 wherein an animal with levelsdifferent than those seen in Tables 5-14 (e.g., up regulated versus downregulated) would be identified as potentially benefiting from feeding acomposition of the present invention.

It is also contemplated herein that the invention relates to methods fortreating an animal suffering from disorders or disease associated withor relating to any one of more of the following biological pathways:blood clotting and platelet activation and aggregation, bone and muscleintegrity, inflammatory responses, cartilage degradation and painresponse, DNA damage and repair pathways, neural function, glycogensynthesis and degradation, glycolysis, gluconeogenesis, the pentosephosphate pathway and electron transport comprising administering to theanimal a composition of the present invention.

This invention is not limited to the particular methodology, protocols,and reagents described herein because they may vary. Further, theterminology used herein is for the purpose of describing particularembodiments only and is not intended to limit the scope of the presentinvention. The terms “comprise”, “comprises”, and “comprising” are to beinterpreted inclusively rather than exclusively.

Unless defined otherwise, all technical and scientific terms and anyacronyms used herein have the same meanings as commonly understood byone of ordinary skill in the art in the field of the invention. Althoughany methods and materials similar or equivalent to those describedherein can be used in the practice of the present invention, thepreferred methods, devices, and materials are described herein.

All patents, patent applications, and publications mentioned herein areincorporated herein by reference to the extent allowed by law for thepurpose of describing and disclosing the compositions, compounds,methods, and similar information reported therein that might be usedwith the present invention. However, nothing herein is to be construedas an admission that the invention is not entitled to antedate suchdisclosure by virtue of prior invention.

In the specification there have been disclosed typical preferredembodiments of the invention and, although specific terms are employed,they are used in a generic and descriptive sense only and not forpurposes of limitation, the scope of the invention being set forth inthe following claims. Many modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims theinvention may be practiced otherwise than as specifically described.

EXAMPLES

This invention can be further illustrated by the following examples ofpreferred embodiments thereof, although it will be understood that theseexamples are included merely for purposes of illustration and are notintended to limit the scope of the invention unless otherwisespecifically indicated.

Example 1

A composition formulated for senior or super senior regular or smallbreed canines is described in Table 2.

TABLE 2 Ingredient Composition for Canine Regular or Small Breed SuperSenior Ingredient % of composition Carbohydrate 65.83 Animal Protein14.31 Vegetable Protein 6.05 Animal/Vegetable Fat 6.60 Omega Fat 3.38Fiber 1.42 Minerals 1.63 Vitamins 0.78

Example 2

A composition formulated for senior or super senior large breed caninesis described in Table 3.

TABLE 3 Ingredient Composition for Canine Large Breed Super SeniorIngredient % of composition Carbohydrate 65.15 Animal Protein 14.79Vegetable Protein 6.45 Animal/Vegetable Fat 6.23 Omega Fat 4.12 Fiber1.30 Minerals 0.91 Vitamins 1.05

Example 3

A composition formulated for senior or super senior felines is describedin Table 4.

TABLE 4 Ingredient Composition for Feline Super Senior Ingredient % ofcomposition Carbohydrate 31.47 Animal Protein 25.57 Vegetable Protein20.14 Animal/Vegetable Fat 13.31 Omega Fat 1.61 Fiber 4.80 Minerals 1.77Vitamins 1.34

Example 4 Genomic Analysis of Control Vs. Super Senior Pet Food

To further characterize the nutritional benefits of the super senior petfood compositions of the present invention, gene expression profilesfrom animals fed the compositions compared to control animals areassayed and the results are described in detail below.

Materials and Methods:

Study Design:

Blood samples are drawn from 9 Beagles according to conventional methodsbefore and after feeding for 14 days on Super Senior K9 diet (a total of18 samples). Each sample taken after the 14 day trial is compared to itsown control.

Isolation of Lymphocytes from Canine Blood

Reagents:

4 ml canine blood, heparin or EDTA tubes, Hank's Balanced Salt Solution(Gibco 14175-095), HEPES buffer (Gibco 15630-080), Accu-Paque (AccurateChemical & Scientific Corp AN3100).

Materials/Equipment:

Transfer pipettes (VWR 14670-147), 14 ml centrifuge tubes w/caps, 9″Pasteur pipettes, 1.5 ml microcentrifuge tubes (VWR 20170-038),centrifuge tube racks, microcentrifuge tube rack, waste container,Beckman Coulter Allegra 25R Centrifuge, SN AJC01J015 EppendorfCentrifuge, 5417C.

Solutions:

Hank's Balanced Salt Solution (HBSS) w/25 mM HEPES buffer solution ismade by adding 12.8 ml of HEPES buffer solution to a 500 ml bottle ofHBSS. Hank's Balanced Salt Solution and Accu-Paque need to be removedfrom the refrigerator and placed at room temperature at least 30 minutesbefore beginning the lymphocyte isolation. Both solutions should beplace back in the refrigerator (4° C.) immediately following their use.

Procedure:

-   -   1. Measure 4 ml of HBSS w/HEPES into the correct number of 14 ml        centrifuge tubes (one tube for each 4 ml draw of blood)    -   2. Using a transfer pipette, transfer 4 ml blood from the        Vacutainer® tubes to the 14 ml centrifuge tube containing the        HBSS w/HEPES.    -   3. Mix the sample well using the transfer pipette to pipette up        and down for 30 seconds.    -   4. Insert a 9″ Pasteur pipette into each of the 14 ml centrifuge        tubes. Make sure the bottom tip of the Pasteur pipette touches        the bottom of the tube.    -   5. Using a transfer pipette, slowly add 4 ml of Accu-Paque by        running the liquid down the inside of the Pasteur pipette        allowing gravity to layer the Accu-Paque under the diluted blood        sample.    -   6. Plug the top of the Pasteur pipette using your finger and        gently remove the pipette.    -   7. Centrifuge the tubes at 800×g for 20 minutes at room        temperature. For puppy blood a longer centrifugation of 45        minutes is necessary to allow for a good separation of RBC's        from WBC's.    -   8. Using a transfer pipette, carefully remove the top layer to        within 0.5 cm of the middle opaque layer and discard.    -   9. Using a new transfer pipette, carefully remove the middle        opaque layer and transfer to a 1.5 ml microcentrifuge tube. Be        careful not to transfer any of the bottom layers.    -   10. Centrifuge the microcentrifuge tubes at 13,200 rpm for 3.5        minutes at room temperature.    -   11. Carefully remove the supernatant and flash freeze the        remaining pellet (lymphocytes) in liquid nitrogen. Store the        final samples at −80° C.        RNA Isolation:        Reagents:

Deionized H₂O, Absolute ethanol (Sigma E7023), RNA Storage Solution(Ambion 7000), RNase Zap® (Ambion 9780), Buffer RLT, Buffer RW1 andBuffer RPE (provided in the RNeasy Mini Kit).

Equipment/Materials:

RNeasy Mini Kit (Qiagen 74104), QIAshredder spin columns (Qiagen 79656),P1000 Pipetman pipette (Rainin), P200 Pipetman pipette (Rainin), 100-100μl filtered pipette tips (USA Scientific 1126-7810), 1-200 μl filteredpipette tips (USA Scientific 1120-8810), sterile transfer pipettes (VWR14670-147), 55 ml sterile solution basin (VWR 21007-974), 2 wastecontainers (one for liquid, one for tips/pipettes), 1.5 ml sterilemicrocentrifuge tubes (VWR 20170-038), Microcentrifuge tube rack,permanent marker, Eppendorf Microcentrifuge, model #5417C.

Procedure:

-   -   1. Loosen the pellet in the microcentrifuge tubes by thawing        slightly and then flick the tube to dislodge the pellet.    -   2. Add the appropriate volume of Buffer RLT (in this case use        600 μl). Vortex or pipette to mix.    -   3. Transfer sample to a QIAshredder tube to homogenize the        sample. Centrifuge for 2 minutes at 14,000 rpm. Discard spin        column but keep the collection tube and its contents.    -   4. Add one volume (600 μl) of 70% ethanol to the homogenized        lysate and mix by pipetting.    -   5. Apply a 600 μl aliquot of the sample to an RNeasy mini column        placed in a 2 ml collection tube. Close tube gently and        centrifuge for 15 sec at 14,000 rpm. Discard the flow-through.        Add the second 600 μl aliquot of the cell lysate to the same        spin column and repeat. Discard flow-through.    -   6. Reuse the collection tube from step 5. Add 700 μl Buffer RW1        to the column. Centrifuge for 15 sec at 14,000 rpm. Discard the        flow-through and collection tube.    -   7. Transfer the column to a new 2 ml collection tube and pipette        500 μl Buffer RPE onto the column. Centrifuge for 15 sec at        14,000 rpm to wash the column. Discard the flow-through but save        the collection tube for step 8.    -   8. Add another 500 ml Buffer RPE to the column. Centrifuge for 2        min at 14,000 rpm to dry the membrane.    -   9. Transfer the column to a new 1.5 ml collection tube. Pipette        10 μl of RNA Storage Solution directly onto the membrane.        Centrifuge for 1 min at 14,000 rpm to elute the RNA. Add a        second volume of 5 μl of RNA Storage Solution directly to the        membrane and spin for an additional minute. Store the final        elution of RNA at −80° C.        RNA Probe Preparation and Hybridization.        Reagent:

Ovation™ Biotin System v1.0 for probe preps.

Protocol:

User Guide (Cat#D01002, version Oct. 27, 2004, NuGEN Technologies, Inc).The experimental procedure is followed as described in the user guide.All probe preparation starts with 50 ng of total RNA.

Genechip Procedures:

The Genechips used for the test is the Canine Genome 2.0 Array(Affymetrix). This Genechip contains 44,000 probe sets. Detailedsequence information for each unique probe identification number isavailable from the manufacturer.

Gene Expression Analysis:

Normalization is performed using MAS 5 provided in GCOS Affymetrixsoftware (version 1.2). Expression levels for the genes analyzed areindicated on the tables included in the examples below, where an upwardfacing arrow refers to “up regulation” or increase and a downward facingarrow indicates “down regulation” in gene expression. Similarly, in sometables, upward or downward facing arrows also indicate increases ordecreases in activity of certain proteins involved in a particularpathway, and are otherwise self explanatory.

Gene List Selection:

15,411 genes are selected for further analysis based on their “present”calls in at least 9 out of 18 samples.

Results of the gene chip analysis indicate that 1088 genes aredifferentially expressed between the control and Super Senior diettreated groups. The expression levels of these 1088 genes arestatistically significant when grouped by ‘diet’; using a parametrictest where the variances is not assumed to be equal (Welch t-test). Thep-value cutoff is 0.01 with no multiple testing correction. Under thoseselection criteria only about 154 genes would be expected to pass therestriction by chance. The genomic data is discussed in detail below.

Results:

Effect of Nutrition on Genes Associated with Pain and Inflammation

Based on an analysis of the gene chip data, at the P<0.01 level, 1,088genes changed compared to control expression levels (10 were upregulated and the rest down regulated). At the P<0.001 level, dataindicate that 35 genes are down regulated in beagles fed the supersenior food. Nine of these down regulated genes are identified asrelated to the inflammatory and pain response. Down regulation of thesegenes may be predicted to result in pain relief, cartilage protection(less damage) and reduction in inflammatory responses. The compositionsdisclosed herein may be part of a therapeutic regimen to treat animalssuffering from pain and/or inflammatory diseases. These genes and theirputative role in inflammation and pain response are provided below inTables 5-6.

TABLE 5 Genes involved in inflammation and pain response (P < 0.001)Sequence Best Current BLAST % match of probe ID No. Genes Also Known AsProbe Annotation sequence to BLAST hit Probe Target Sequence 1Phospholipase IPLA2GAMMA, CfaAffx.6431.1.S1_s_at PREDICTED: Canis 100GGAGCCATGCATTTTAT A2 IPLA2-2 familiaris similar to GACAGTCAAACGTGGGAintracellular membrane- AAATATTCTTAAGGACA associated calcium-GAATGGGATCCTCGCTA independent ATGATTGAAACAGCAAG phospholipase A2 gamma;AAACCCTTCATGTCCTA transcript variant 3 AGGATGGAGGTTTGCTT(LOC475380); mRNA CTGAATAACCCTTCAGC GCTAGCAATGCACGAGT GCAAATGTCTTTGGCCTGACGTCCCATTAGAGTG CATTGTGTCCCTGGGCA CCGGGCGTTATGAGAGT GATGTGAGAAACTCTGTGACATCTACAAGCTTGA AAACCAAACTGTCTAAT GTCATTAACAGTGCTAC AGATACAGAAGAAGTCCACGTAATGCTTGATGGT CTTTTACCTCCTGACAC CTATTTTACAT 2 Dipeptidase PutativeCfaAffx.31124.1.S1_at PREDICTED: Canis 82.197 GTGCTGCAATGCAACCT 2dipeptidase familiaris similar to GTTAGCTAACGTGTCCA dipeptidase 2CTGTGGCAGTTCCCACG (LOC611083); mRNA CATCCCTGCCCTGGAAG CCCCACAGTGCTGACTCTCCATCCCTCAGATCAC TTTGACTACATCAGGGC AGTCATTGGATCCAAGT TCATTGGAATTGGTGGAGATTATGATGGGGCCAG ACGTTTCCCTCAGGGGC TGGAGGATGTGTCCACA TACCCAGTTCTGATAGAGGAGTTGCTGAGGCGT GGCTGGAGTAGGGAAG AGCTCCAGGGTGTCCTT CGAGGAAACCTACTGCGGGTCTTTGGACAGGTGG AACAGGTACGGGAGGC AAGCAAGGGGCAAAGG CCCTTGGAGGATGAGTTCCCGGATGAGCAGCTG AGCAGCTCTTGCCGCTC CGTTCTCTCACGTCTGC ATCAGACACAGTACCCTGCTCCATACCAGAAACT AACTGAGATTTCACCTG AGTGGTCCCCTAAACAG TCATTGTCAAAATCTCTCCCCATCATGGCCCCAGG CCTCATAGTTATTGCTG CTTGT 3 Thromboxane Thromboxane ACfaAffx.6939.1.S1_s_at PREDICTED: Canis 100 ATCGCTGGCTATGAGAT synthasesynthase 1, familiaris similar to CATCACCAACACGCTCT Thromboxane AThromboxane-A synthase CTTTTGCCACCTACCTC synthase. Platelet,(TXA synthase)(TXS) CTGGCCACCAACCCTGA Cytochrome P450. (LOC482771); mRNACTGCCAAGAGAAGCTTC subfamily V. TGGCAGAGGTGGACAG CYP5. CYP5A1,CTTTAAGGAGAAATATA Thromboxane CGGCCCTTGACTACTGC synthatase, TXAAGCCTCCAGGAAGGCCT synthase, TXS GCCCTACCTGGACATGG TGATTGCGGAGACCTTGAGGATCTACCCCCCGGC TTTCAGGTTCACACGGG AGGCGGCGCGGGACTG CGAGGTGCGGGGACAGCGCATCCCCGCGGGCG CCGTGGTGGAGGTGGC CGTGGGCGCCCTGCAC CGTGACCCTGAGTACTGGCCACAACCGGAGACCT TCAACCCCGAGAGGTTC AAGGCCGAGGCGCAGC GACGACAGCAACCCTTCACCTACCTGCCGTTCGG CGCGGGCCCCCGGAGC TGCCTCGGGGTGCGGC TGGGGCTGCTGGAGGTCAAGCTGACGCTGCTGC AGGTCCTGCACCAGTTC CGGTTCGAGGCCTGCC CGGAGACGCAGGTACCACTGCAGCTAGACTCCA AATCTGCCCTAGGTCCA AAGAATGGCATCTACAT CAAGATTGTCTCCCGCT4 Ubiquitin Ubiquitin protein CfaAffx.275.1.S1_s_at PREDICTED:  97.19626GATTTGGCCCGTGACCC conjugating ligase. Ubiquitin PantroglodytesTCCAGCACAATGTTCTG enzyme carrier protein, LOC461941 CAGGTCCTGTTTGGGATE2D 3 E2(17)KB 3, (LOC461941); mRNA GATATGTTTCATTGGCA UbiquitinAGCCACAATTATAGGAC conjugating CTAATGACAGCCCATAT enzyme E2-17 CAAGGkDa 3, UBC4/5, UBCH5C 5 NEDD8 Neural precursor Cfa.12556.1.A1_s_atPREDICTED: Canis 99.12473 GGAATGGGCTACTCTAC ultimate cell expressed.familiaris similar to NEDD8 TCATGCAGNCAAGCAGG buster-1 developmentallyultimate buster-1 (NY- NCCTGCATCAGGCCAGT down regulated 8,REN-18 antigen) GGGAACCTGGACGAAG Ubiquitin like (LOC475542); mRNACCCTGAAGATTCTTCTC protein NEDD8 AGCAATCCTCAGATGTG GTGGTTAAATGATTCAGATCCTGAAACGANCAAC CAGCAAGAAAGTCCTTC CCAGGAAAACATTGACC AACTGGTGTACATGGGCTTCGACGCTGTGGTGGC TGATGCTGCCTTGAGAG TGTTCAGGGGAAACGTG CAGCTGGCAGCTCAGNCCCTCGCCCACAACGGA GGAACTCTTCCTCCTGA CCTGCAGCTCTTGGTGG AAGACTCTTCATCAACGCCATCCACGTCCCCTTC CGACTCCGCAGGTACCT CTAGTGCCTCAACAGAT GAAGATATGGAAACCGAAGCTGTCAATGAAATAC TGGAAGATATTCCAGAA CATGAAGAAGATTATCTT GACTCAACACTGGAAG6 Mitogen - p38, Mitogen CfaAffx.2947.1.S1_at Homo sapiens mitogen-97.84946 GAGATGGAGTCCTGAGC activated activated proteinactivated protein kinase ACCTGGTTTCTGTTTTGT protein kinase 14,14; transcript variant 2; TGATCCCACTTCACTGT kinase CytokinemRNA (cDNA clone GAGGGGAAGGCCTTTTC 14 (p38) suppressive MGC: 34610ATGGGAACTCTCCAAAT antiinflammatory IMAGE: 5181064); ATCATTC drug bindingcomplete cds protein 1, CSBP1, CSAID binding protein 1. Stressactivated protein kinase 2A, SAPK2A, p38 MAP kinase, p38alpha, RK, MXI2, Cytokine suppressive antiinflammatory drug bindingprotein 2, CSBP2. CSAID binding protein 2 7 Matrix MMP 19Cfa.4573.1.A1_at Homo sapiens cDNA 48.93048 GTAGTTGATTCCTGGTTmetalloproteinase FLJ38021 fis; clone CGCCTTTCCTCTTGGGT 19 (MMP-19)CTONG2012847 CCCATAGGTTCGAATCC CCTTCTACCTCAGTCGG GAGTACTGTCCTCCATGGTGCTTCCCTTCCTCTC CTTAATGTGGGGAAGAC CATGGGGCAATGCATGG CGCAGGACCTGCCTCCCCCAAAAGCAGTCTACT TGCTCCACGGAGAGAGA ACTGGGTCCACGTGCCA GAGTCTTGCCCTTTGGCCCAGAGTAGCCTGGTCT TCATGGCTGTATGGGAG ACAAGTGCCTTCTCTGC TTCTTGTTGTAGGTGATGCTAATCTCCTTAACCA AACCTTTGTCCCAGCCG CTAATCTGTTCTAACTCT CCCTCCTCNTGATTCTCCTGCTCAAAGTCTGTTC 8 Tissue TIMP-1 Cfa.3680.1.S1_s_atCanis familiaris TIMP 99.4 AGATGTTCAAGGGTTTC Inhibitormetaliopeptidase inhibitor AGCGCCTTGGGGAATG of 1 (TIMP1); mRNACCTCGGACATCCGCTTC metalloproteinase GTCGACACCCCCGCCCT s (TIMP-1)GGAGAGCGTCTGCGGA TACTTGCACAGGTCCCA GAACCGCAGCGAGGAG TTTCTGGTCGCCGGAAACCTGCGGGACGGACAC TTGCAGATCAACACCTG CAGTTTCGTGGCCCCGT GGAGCAGCCTGAGTACCGCTCAGCGCCGGGGC TTCACCAAGACCTATGC TGCTGGCTGTGAGGGG TGCACAGTGTTTACCTGTTCATCCATCCCCTGCA AACTGCAGAGTGACACT CACTGCTTGTGGACGGA CCAGTTCCTCACAGGCTCTGACAAGGGTTTCCAG AGCCGCCACCTGGCCT GCCTGCCAAGAGAGCC AGGGATATGCACCTGGCAGTCCCTGCGGCCCCG GATGGCCTAAATCCTAC TCCCCGTGGAAGCCAAA GCCTGCACAGTGTTCACCCCACTTCCCACTCCTG TCTTTCTTTATCCAAAA 9 Fatty OleamideCfaAffx.7308.1.S1_x_at PREDICTED: Canis 63.33333 GAAGTGGAGTAGGTGC acidhydrolase familiaris similar to CGCTGTTGCTGCTGGTG amide AnandamideUbiquinol-cytochrome c TTGAATTCAGAACTGTA hydrolase amidohydrolasereductase complex 11 kDa GCGGGACATGGGGCTG (FAAH) FAAHprotein; mitochondrial GAGGACGAGCAAAAGAT precursor (MitochondrialGCTGACCGGGTCCGGA hinge protein)(Cytochrome GATCCCAAGGAGGATCCC1; nonherne 11 kDa CCTAACAACAGTGAGAG protein)(Complex IIIAGCAATGCGAGCAGCTG subunit VIII); transcript GAGAAATGTGTAAAGGCvariant 2 (LOC608530): TCGGGAGCGGCTAGAG mRNA CTCTGTGACCAGCGTGTATCCTCCAGGTCACAGA CAGAGGAGGATTGCACA GAGGAGCTCTTTGACTT CCTGCATGCAAGGGACCACTGTGTGGCCCACAAA CTCTTTAACAGCTTG

TABLE 6 Summary of down-regulated enzyme roles involved in theeicosanoid pathway (inflammatory response) Gene Expression Compared Geneto Control Results in Role Phospholipase A₂ ↓ ↓ in arachidonic ↓ in2-series inflammatory release from response phospholipids Thromboxanesynthase ↓ ↓ Thromboxane A₂ ↓ platelet aggregation, vasoconstriction,lymphocyte proliferation and bronchoconstriction ↓ ↓ Thromboxane B₂ ↓vasoconstriction Dipeptidase 2 ↓ ↓ Leukotriene E₄ ↓ component ofslow-reactive substance of anaphylaxis, microvascular vasoconstrictorand bronchoconstriction Ubiquitin conjugating ↓ ↓ ubiquination or ↓ MMPProduction enzyme E2D 3 activation of TAK 1, (and NEDD8 ultimate IRAKand TRAF buster-1) Mitogen activated ↓ ↓ in c-Jun promotor ↓ MMPProduction protein kinase 14 (p38) MMP-19 ↓ ↓ MMP- 19 ↓ in T-cellderived MMP-19 which has been implicated in rheumatoid arthritis TIMP-1↓ ↓ TIMP-1 Deactivates MMP′s concentration is directly related to MMPconcentration Fatty acid amide ↓ ↑ anandmide ↓ pain response hydrolaseEffect of Nutrition on Genes Involved in Heart Health and BloodCoagulation

At the P<0.001 and P<0.01 level, 12 genes are identified to be relatedto heart health through regulation of the eicosanoid pathway and bloodcoagulation pathway. The genes are responsible for blood coagulationthrough platelet activation and aggregation. The down regulation ofthese genes through nutrition can prevent inappropriate blood clottingwhich may result in heart or brain related disorders. The compositionsof the present invention may be part of a therapeutic regimen to treatanimals suffering from disorders or diseases of the blood, heart orbrain. These genes and their putative role in vivo are described inTables 7 and 8 below.

TABLE 7 Genes involved in heart health and blood coagulation % match ofSequence probe sequence ID No. Gene Probe P-valueBest current BLAST annotation to BLAST hit Probe Target Seq. 10Glycoprotein lb Cfa.3503.1.S1_at <0.01 Canis familiaris glycoprotein lb98.57143 TGTGGGTCCGAGCTAACAGCTACGTGGGG mRNA; complete cdsCCTCTGATGGCAGGACGGCGGCCCTCTGC CCTGAGCCTGGGTCGTGGGCAGGACCTGCTAGGTACGGTGGGCGTTAGGTACTCCAGC CACAGCCTCTGAGGCGACGGTGGGCAGTTTGGGGACCTTGAGAGGCTGTGATGGGCCC TCCTATCAGGATCTTGCTGGGGGTGGGTGGGCAGGGAGCACAGGATTGGGGGGAGGC CTTAAGCACCTTTTCTGGGTCAGAAGCCTCCTCTCCGCATTGCATGTGCAACCTCAGTGA AGCAGCATGGGCAGGGGAGCCGGACGGGCCACCCAACAGAGCTCCTTATGCTGCAGGA GGGGTTCACAGACCACTCGGACATCACCATCACCTTGGGGGGGGTGCTTGAGGGAAAAG CAAATTGAACAGAGCGTGATTCTCACGTGCAGGTACCTAAGGGAACTGGGGAAGAGATG CACCAAGACGAGAGCCCTCGTCATCCCTGGGGAGCCCAAGCCTAGGGGTTTTCTTCCTC TTCCCGTTTAGCATTTTCCACCATCGTATGT TAC 11Platelet CfaAffx.4809.1.S1_at <0.01 PREDICTED: Canis familiaris similar50 AGTTTTGACCAATTCGCTCTGTACAAGGAG glycoprotein VIto glycoprotein VI (platelet) GGGGACACTGAGCCCCACAAGCAATCTGC(LOC484303); mRNA AGAACAGTACTGGGCCAATTTCCCCATCACCGCAGTGACTGTTGCCCACAGTGGGATCTA CCGATGCTATAGCTTTTCCAGCAAGTTCCCGTACCTGTGGTCAGCCCCCAGCGACCCCC TGGAGCTTGTGGTAACAGGTGAGGGAGATGCAGTCCAAGCCTTTCTTCTTCAGCTCTTG CATACTCTGGTGGAAGTTCCAGGGGAGGGGCCAACAGTGCCTTCTAGGACTATCACTGT CTCTCCAAAGGGGTCAGACTCTCCAACTGGTCTTGCTCACCAGCACTACACCAAGGGCAA TCTGGTCCGGATATGCCTTGGAGCTGTGATTCTAATACTCCTGGTGGGAATTCTGGCAGA AGATTGGCACAGCAGAAAGAAACCCCTGTTGCTCCGGGTCAGAGCTGTCCACAGGCCAC TCCCACCCCTCCCACAGACCCAGAAACCACACAGTCATCAGGATGGGGGTCGACCAGAT GGCCATAACCAT 12 PlateletCfaAffx.7430.1.S1_at <0.01 PREDICTED: Canis familiaris similar 100TCTGGGCTGCCACGGAGGCCACCAACGAC glycoprotein IXto Platelet glycoprotein IX  TGCCCCGCAGAGTGCACCTGCCAGACCCT precursorprecursor (GPIX)(CD42A) GGAGACCATGGGGCTGTGGGTGGACTGCA (LOC609630); mRNAGGGGGCGGGGACTCAAGGCCCTGCCCGC CCTGCCGGTCCACACCCGCCACCTCCTGCTGGCCAATAACAGCCTCCGCTCCGTGCCC CCTGGTGCCTTCGACCACCTGCCTGGGCTGCAGATCCTCGACGTGATGCACAACCCCTG GCACTGTGACTGCAGCCTCACCTACCTGCGTCTCTGGCTGGAGGACCACACGCCCGAGG CCTTGCTGCAGGTCCGCTGTGCCAGCCCCGCGCTGGCCACCACCCGGCCGCTGGGCTG GCTGACGGGCTACGAGCTGGGCAGCTGCGGCTGGCAGCTACAGGCACCCTGGACCTA 13 Coagulation CfaAffx.14964.1.S1_s_at<0.01 PREDICTED: Canis familiaris similar 99.6008ATCTCTCAGGCAACATCGTCTTCTACACCG factor XIII Ato Coagulation factor XIII A chain GGGTCTCCAAGACGGAATTCAAGAAGGAGchain precursor precursor (Coagulation factor XIIIa)ACATTTGAAGTGACACTGGAGCCCTTGTCT (Protein-glutamine gamma-TTCAAGAGAGAGGAGGTGCTGATCAGAGC glutamyltransferase A chain)GGGCGAGTACATGGGCCAGCTGCTAGAGC (Transglutaminase A chain);AAGCATACCTGCACTTCTTTGTCACAGCGC transcript variant 1 (LOC478711);GTGTCAATGAGTCCAAGGATATTCTGGCCA mRNA AGCAGAAGTCCACCGTGCTGACGATCCCCCAGCTCATCATCAAGGTCCGTGGCGCCAA GATGGTTGGTTCTGACATGGTGGTGACAGTTGAGTTCACCAATCCCCTGAAAGAAACTCT GCGGAATGTGTGGATACACCTGGATGGTCCTGGAGTGATAAAGCCAATGAGGAAGATGT TCCGTGAAATCCAGCCCANTGCCACCATACAATGGGAAGAAGTGTGTCGACCCTGGGTG TCTGGCCGTCGGAAGCTGATAGCCAGCATGACGAGTGACTCCCTGAGACACGTGTATG 3 Thromboxane CfaAffx.6939.1.S1_s_at<0.001 PREDICTED: Canis familiaris similar 100ATCGCTGGCTATGAGATCATCACCAACACG synthase to Thromboxane-A synthase (TXACTCTCTTTTGCCACCTACCTCCTGGCCACC synthase)(TXS)(LOC482771);AACCCTGACTGCCAAGAGAAGCTTCTGGCA mRNA GAGGTGGACAGCTTTAAGGAGAAATATACGGCCCTTGACTACTGCAGCCTCCAGGAAGG CCTGCCCTACCTGGACATGGTGATTGCGGAGACCTTGAGGATCTACCCCCCGGCTTTCAG GTTCACACCGGAGGCGGCGCGGGACTGCGAGGTGCGGGGACAGCGCATCCCCGCGG GCGCCGTGGTGGAGGTGGCCGTGGGCGCCCTGCACCGTGACCCTGAGTACTGGCCAC AACCGGAGACCTTCAACCCCGAGAGGTTCAAGGCCGAGGCGCAGCGACGACAGCAACCC TTCACCTACCTGCCGTTCGGCGCGGGCCCCCGGAGCTGCCTCGGGGTGCGGCTGGGG CTGCTGGAGGTCAAGCTGACGCTGCTGCAGGTCCTGCACCAGTTGGGGTTCGAGGCCT GCCCGGAGACGCAGGTACCACTGCAGCTAGACTCCAAATCTGCCCTAGGTCCAAAGAAT GGCATCTACATCAAGATTGTCTCCCGCT 14Dystrobrevin CfaAffx.15541.1.S1_s_at <0.01PREDICTED: Canis familiaris similar 99.65986GGCAACATGTCGTCCATGGAGGTCAACATC binding protein 1to dystrobrevin binding protein 1 GACATGCTGGAGGAGATGGACCTGATGGAisoform a isoform a (LOC610315); mRNA CATCTCTGACCAGGAGGCCCTGGACGTCTTCCTGAACTCCGGCGCTGAAGACAACACGG TGCCGTCTCCGGTCTCAGGGGCTGGCTCGGGGGACAGTCGGCAGGAAATCACGCTCCG GGTTCCAGATCCCGCCGAATCGCAAGCTGAGCCTCCTCCCTCGCCGTGTGCCTGTCCTG AGCTGGCCCCCCCGGCCCCCGGCGACGGTGAGGCCCCCGTGGTCCAGTCTGACGAGG AG 15 integrin beta-7 Cfa.11961.1.A1_s_at<0.01 PREDICTED: Canis familiaris similar 99.0909ATTACAACGTGACTCTGGCTTTGGTCCCTG precursor to integrin beta-7 precursorTCCTGGATGACGGCTGGTGCAAAGAGAGG (LOC477598); mRNAACCCTAGACNAACCAGCTGCTGTTCTTCCT GGTGGAGGAGGAANCCGGAGGCATGGTTGTGTTGACAGTGAGACCCCAAGAGAGAGGC GCGGATCACACCCAGGCCATCGTGCTGGGCGTGTAGGGGGCATCGTGGCAGTGGGGC TGGGGCTGGTCCTGGCTTACCGGCTCTCTGTGGAAATCTACGNCCGCCGAGAATTTAGC CGCTTTGAGAAGGAGCAGAAGCACCTCAACTGGAAGCAGGAAAACAATCCTCTCTACAGA AGCGCC 16 integrin-linkedCfa.465.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar 100TGGGCGCATGTATGCACCTGCCTGGGTGG kinase to integrin linked kinase; CCCCTGAAGCTCTGCAGAAGAAGCCTGAA transcript variant 1GATACAAACAGACGCTCAGCAGATATGTGG (LOC476836); mRNAAGTTTTGCAGTGCTTCTGTGGGAACTGGTG ACGAGGGAGGTACCCTTTGCTGACCTCTCCAACATGGAGATTGGAATGAAGGTGGCACTG GAAGGCCTTCGGCCTACTATCCCACCAGGCATTTCCCCCCATGTGTGTAAGCTCATGAA GATCTGCATGAATGAAGACCCTGCTAAGCGGCCCAAGTTTGACATGATTGTGCCTATCCT GGAGAAGATGCAGGACAAGTAGAGCTGGAAAGCCCTTGCCTAAACTCCAGAGGTGTCAG GACACGGTTAGGGGAGTGTGTCTCCCCAA AGCAGCAGGC17 Thrombospondin Cfa.21204.1.S1_at <0.01PREDICTED: Canis familiaris similar 54.83871ATACGAATGCAGAGATTCCTAATCAAACTGT 1 to thrombospondin 1 precursorTGATCAAAAGACTGATCCTAACCAATGCTG (LOC487486); mRNAGTGTTGCACCTTCTGGAACCACGGGCTTAA GAAAACCCCCAGGATCACTCCTCCCTGCCTTTTCTCTGCTTGCATATCATTGTGGACACCT AGAATACGGGACTTGCCTCGAGACCATGCNNNNNTCCAAATCAGACTNNNNNNGTAGCCT CTGAACGCGAAGAGAATCTTCCAAGAGCAT GAACAG 18Thrombospondin CfaAffx.18675.1.S1_s_at <0.01PREDICTED: Canis familiaris similar 100 GAAGCCCTTGATGGATACTGTGAACGGGAArepeat containing to extracellular matrix protein 1CAGGCTATAAAGACCCACCACCACTCCTGT 1 isoform 1 precursor (LOC608791);TGCCACCACCCTCCTAGCCCTGCCCGCGA mRNA TGAGTGCTTTGCCCGTCAGGCGCCATACCCCAACTATGACCGGGACATCCTGACCCTTGA TTTCAGCCAAGTTACCCCCAACCTCATGCAACATCTCTGTGGAAATGGAAGACTTCTCAC CAAGCATAAACAGATTCCTGGGCTGATCCGGAACATGACTGCCCACTGCTGTGACCTGCC ATTTCCAGAGCAGGCCTGCTGTGCTGAGGAGGAGAAATCGGCCTTCATTGGAGACTTGTG TGGTTCCCGACGTAACTTCTGGCGAGACTCTGCCCTCTGCTGTAACCTGAATCCTGGAGA TGAACAGACCAACTGCTTCAACACTTATTATCTGAGGAATGTGGCTCTAGTGGCTGGAGA CAAT 19 ThrombospondinCfaAffx.16594.1.S1_at <0.01 PREDICTED: Canis familiaris similar 98.13084TGGTTGTAGCTCCTCACTTGTCCAAGACCG type 1 motif, 17to lines homolog 1 isoform 1 AAGCAGCAACCAAACTGAACTTAGCCTTTG(LOC607902); mRNA GGCTGCTCTTGGTAGTCACAGAAATGCCCACGCTTCAGTCCCCTGGGCTTCCAATGCTTC TGGACCTCTGAACCAGCCTGTGATGTCCAAGGAACCCCACGTCACGCTCCAGGCTGCTG CTGGTCTGTCTCCCCCACAAGCTTCTCAAAGTCTGGTAGATTATGACAGCTCTGATGATT CTGAAGTAGAAGTCACAGACCAGCACTCAACAAACAGTAAACAAACATCTTTACAGCAAGA AGCAAAGAAGAAATTTCAGGACACAGTTAGAACAGGTCCAGATGAAAAAGAACTTAGCAT GGAGCCTCAATCAAGGCCTCTGGTTCCAGAACAATCTAATATTAATATTCCCTTCTCTGTT GACTGTGACATCTCCAAAGTAGGAATATCTTACAGGACACTGAAGTGCTTTCAGGAGCTA CAGGGTGCCATTTACCGTTTGCAGAAAAAAAATCTTTTCCCCTATAATGCCACA 20 Angio-associated Cfa.8616.1.A1_s_at <0.001Canis familiaris angio-associated 64.77273GCGGACTGTGTTCCAACCCCTTCAGCCGAC migratory cellmigratory cell protein (AAMP) gene; TTGCCCCCTCCGTCCCTTCTCTTAAGAGACprotein (AAMP) complete cds CCATCCCTTGGCCCCCCACCCCACCCTCACCCAGACCTGCGGGTCCCTCAGAGGGGGGT CAGGCCTCTTTCTCTTTCACCTTCATTTGCTGGCGTGAGCTGCGGGGGTGTGTGTTTGTA TGTGGGGAGTAGGTGTTTGAGGTTCCCGTTCTTTCCCTTCCCAAGTCTCTGGGGGTGGA AGGAGGAAGAGATATTAGTTACAGA

TABLE 8 Summary of down regulated enzyme roles involved in heart healthand blood coagulation Gene Expression compared Gene to Control RoleGlycoprotein Ib ↓ GP-Ib, a surface membrane protein of platelets,participates in the the formation of platelet plugs by binding to the A1domain of von Willebrand factor, which is already bound to thesubendothelium, Platelet glycoprotein VI ↓ Collagen receptor belongingto the immunoglobulin-like protein family that is essential for plateletinteractions with collagen Platelet glycoprotein IX ↓ The GPIb-V-IXcomplex precursor functions as the von Willebrand factor receptor andmediates von Willebrand factor - dependent platelet adhesion to bloodvessels. The adhesion of platelets to injured vascular surfaces in thearterial circulation is a critical initiating event in hemostasisCoagulation factor XIII A ↓ Factor XIII is activated by chain precursorthrombin and calcium ion to a transglutaminase that catalyzes theformation of gamma- glutamyl- epsilon-lysine cross-links between fibrinchains, thus stabilizing the fibrin clot. Thromboxane synthase ↓ ↓platelet aggregation, vasoconstriction, lymphocyte proliferation andbronchoconstriction Angio-associated ↓ contains a heparin-bindingmigratory domain (dissociation cell protein (AAMP) constant, 14 pmol)and mediates heparin-sensitive cell adhesion Dystrobrevin binding ↓Plays a role in the protein 1 isoform a biogenesis of lysosome- relatedorganelles such as platelet dense granule and melanosomes Thrombospondin1 ↓ Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrixinteractions. Can bind to fibrinogen, fibronectin, laminin, type Vcollagen and integrins alpha-V/beta-1, alpha- V/beta-3 andalpha-IIb/beta- 3. Thrombospondin type 1 ↓ Metalloprotease activitymotif, 17 Thrombospondin repeat ↓ containing 1 Integrin beta-7 precursor↓ Integrin alpha-4/beta-7 (Peyer's patches-specific homing receptorLPAM-1) is expected to play a role in adhesive interactions ofleukocytes. It is a receptor for fibronectin and recognizes one or moredomains within the alternatively spliced CS-1 region of fibronectin.Integrin alpha-4/beta-7 is also a receptor for MADCAM1 and VCAM 1. Itrecognizes the sequence L-D-T in MADCAM 1. Integrin alpha-E/beta-7(HML-1) is a receptor for E - cadherin. Integrin linked kinase ↓Receptor-proximal protein kinase regulating integrin- mediated signaltransduction. May act as a mediator of inside-out integrin signaling.Focal adhesion protein part of the complex ILK-PINCH. This complex isconsidered to be one of the convergence points of integrin- and growthfactor-signaling pathway. Could be implicated in mediating cellarchitecture, adhesion to integrin substrates and anchorage-dependentgrowth in epithelial cells. Phosphorylates beta- 1 and beta-3 integinsubunit on serine and threonine residues, but also AKT1 and GSK3B.Effect of Nutrition on Genes Involved with Muscle and Bone Regulation

Ten down regulated genes are identified as related to body compositionthrough regulation of bone and muscle. The genes spare muscle and bonedeterioration by reducing nitric oxide production and glucocorticoiddegradation of muscle. Down regulation of these genes results in adecrease in nitric oxide production and glucocorticoid response. Thecompositions disclosed herein may be part of a therapeutic regimen totreat animals suffering from diseases or disorders associated with orrelating to muscle or bone. These genes and their putative role inmuscle and bone regulation are detailed in Tables 9 and 10 below.

TABLE 9 Genes involved in muscle and bone regulation % match of probeSequence ID No. Gene Probe P-value Best current BLAST annotationsequence to BLAST hit Probe Target Sequence 21 Capping Cfa.1044.1.S1_at0.001 PREDICTED: Canis 44.87179 AGGTCCCGTAACACCGGCATCGCGACCGCACA Proteinfamiliaris similar to F-   GCGGCATCTCCCCAGAATAAAGCCCAGTAAACactin capping protein ACCCCTGNNNNNNANNNNNANNNNNCACCACG beta subunitTTTTGCTATCAGAACTCTCCTTGTTTCCAGAGC (LOC478209); mRNACCGTGTGCTTTTGTTTGCCCCAGCCCC 22 Calmodulin Cfa.4168.1.S1_at 0.01PREDICTED: Canis 52.54237 CCACCCATGGTGACGATGACACACATCCTGGTfamiliaris similar to   GGCATGCGTGTGTTGGTTTAGCGTTGTCTGCGcalmodulin 1; transcript TTGTACTAGAGCGAAAATGGGTGTCAGGCTTGTvariant 3 (LOC480416); CACCATTCACACAGAAATTTAAAAAAAAAAAAAA mRNAAANNNNGANAAAAAACCTTTACCAAGGGAGCAT CTTTGGACTCTCTGTTTTTAAAACCTCCTGAACCATGACTTGGAGCCAGCAGATTAGGCTGTGGC TGTGGACTTCAGCACAACCATCAACATTGCTGATCAAGAAATTACAATATACGTCCATTCCAAGTT 23 Dynein Cfa.4942.1.A1_s_at 0.001PREDICTED: Canis 99.6016 ATACCTCAGAGGTCTCGTAGCTCGTGCCCTTGfamiliaris similar to   CCATCCAGAGCTGGGTGGNAGAGACCTGAGAAdynein; cytoplasmic; GGAGGCTCTTTTCTCTGATACACTCGACCTGTCheavy polypeptide 2; AGAACTCTTCCACCCAGACACATTTCTCAATGCtranscript variant 2 TCTTCGCCAGGAAACAGCAAGGGTGATGGGCT (LOC479461); mRNAGCTCTGTGGATAGCCTTAAGTTTGTAGCTTCGT GGAAAGGTCGGCTGCAAGAAGCAAAGCTGCAGATCAAGATGGGCGGCTTGCTTCTGGAAGGCTG CAGTTTTGACGGGAGCCGGCTCTCTGAAAACCACCACGATTCTCCAAGTGTGTCACCAGTTCTCC CTTGCTGTGTTGGCTGGATTCCCCAGGGTGCATATGGTCCCTATTCTCCTGACGAGTGCATATCT CTGCCCGTGTACACGAGCGCTGAGAGGGATCGTGTGGTAGCCAACATCGACGTCCCGTGTGGGG GCANCCAAGACCAGTGGATTCAGTGTGGAGCCGCTCTGTTTCTAAAAAA 24 Dynactin Cfa.1807.1.S1_at 0.01 PREDICTED: Canis 100AGGACGACAAGGCTCAGGACGCAAAGTGTGAA familiaris similar to  ACTGCCTTTGTAACAGGGCAGAAGCAGCTCTG dynactin 3 isoform 2;TATTGGATTCACAACCTACCTATCTGCATTCAG transcript variant 1GTGGGGCTCGGAGGTCAGAGGTCTGGCTACTT (LOC474750); mRNA GAGGTTTGCTGTTTGCAC 25Kinesin Cfa.10496.1.S1_s_at 0.01 PREDICTED: Canis 99.73046AGCCACAGCATTTCCTTTTAACTTGGTTCAATTT familiaris similar to  TTGTAGCAAGACTGAGCAGTTCTAAATCCTTTG Kinesin-like proteinCGTGCATGCATACCTCATCAGTGNACTGTACAT KIF2(Kinesin-2)(HK2);ACCTTGCCCTCTCCCAGAGACAGCTGTGCTCA transcript variant 5CCTCTTCCTGCTTTGTGCCTTGACTAAGGCTTT (LOC478071); mRNATGACCCTAAATTTCTGAAGGACAGCCAAGATAA AGTACATTCCTTAATTGTCAGTGTAAATTACCTTTATTGTGTGTACATTTTTACTGTACTTGAGACAT TTTTTGTGTGTGACTAGTTAATTTTGCAGGATGTGCCATATCATTGAATGGAACTAAAGTCTGTGAC AGTGGACATAGCTGCTGGACCATTCCATCTTACATGTA 26 Heat CfaAffx.11022.1.S1_s_at 0.01 PREDICTED: Canis 100GGTGCTACTGTTTGAAACAGCTCTACTCTCCTC Shock familiaris similar to Heat CGGCTTCTCACTGGAGGATCCCCAGACTCACT Protein 1 shock protein HSP 90-CCAACCGCATTTACCGCATGATAAAGCTAGGC (HSP90) beta(HSP 84)(TumorCTGGGCATCGATGAAGATGAAGTGGCAGCGCA specific transplanatationGGAACCCAGTGCTGCTGTTCCTGATGAGATCC 84 kDa antigen)(TSTA)CTCCACTTGAGGGTGATGAGGATGCCTCTCGC (LOC611252); mRNA ATGGAAGAAGTC 27PPlase CfaAffx.1740.1.S1_at 0.01 PREDICTED: Canis 100GACATCACCAGTGGAGACGGCACCGGCGGTAT familiaris similar to  AAGCATTTATGGTGAGACGTTTCCAGATGAAAA Peptidyl-prolyl cis-transCTTCAAACTGAACCATTATGGCATTGGTTGGGT isomerase C(PPlase)CAGCATGGCCAACGCTGGGCCTGACACCAACG (Rotamase)GCTCTCAGTTCTTTATCACCTTGACCAAGCCCA (Cyclophilin C)CTTGGTTGGATGGCAAACATGTGGTATTTGGAA (LOC481480); mRNAAAGTCCTTGATGGAATGACTGTGGTCCACTCCA TAGAACTTCAGGCAACCGATGGGCACG 28Calcinuerin Cfa.19761.1.S1_at 0.001 PREDICTED: Canis 98.83382GAATTAACAATCTGCTTGAGCCCCAAAACACTA familiaris similar to  CTTATGCACTTCACTTGCCAAAAGATTTGNGCA protein phosphatase 3AGGTTTTGTACCCTGGTAAATGATGCCAAAGTT (formerly 2B); catalyticTGTTTTCTGTGGTGTTTGTCAAATGTTCTATGTA subunit; beta isoformTAATTGACTGTCTGTAACATGCTGTTTNCTTCCT (calcineurin A beta);CTGCAGATGTAGCTGCTTTCCTAAATCTGTCTG transcript variant 5TCTTTCTTTAGGTTAGCTGTATGTCTGTAAAGT (LOC479248); mRNAATGTTAAATTAAATTACTCTATCAGACGCTTGTC TGTCTTTTGATGTAGAAGCAACTTTGTAGCACCTTGTTTTGAGGTNNGCTGCATTTGTTGCTGTAC TTTGTGCAT 29 ProteinCfaAffx.408.1.S1_s_at 0.01 PREDICTED: Canis 99.64664TTCAGTTCCTGTCTCATGGCCGCTCCCGGGAC kinase C familiaris similar to  CATGCCATCGCCGCCACTGCCTTCTCCTGCAT myeloid-associatedCGCTTGTGTGGCTTATGCCACCGAAGTGGCCT differentiation markerGGACCCGGGCCCGTCCCGGAGAGATCACCGG (LOC611521); mRNACTACATGGCCANTGTGCCGGGCCTGCTCAAGG TGCTGGAGACCTTTGTGCCCTGCATCATCTTCGCCTTCATCAGCAACCCCTCCCTGTACCAGCAC CAGCCGGCCCTGGAGTGGTGTGTGGCCGTCTACTCCATCTGTTTCATCCTGGCGGCTGTGGCCAT CCTACTGAACCTGGGGGACTGCACCAACATGCTGCCCATCTCCTTCCCCAGTTTCCTGTCGGGC CTGGCCCTGCTCTCCGTCCTGCTGTATGCCACGGCTCTGGNTCTGTGGCCGCTCTACCAGTTCA ACGAGAAGTATGGTGGCCAGCCCCGTCGGTCGAGGGATGTTAGCTGCGCCGACAGGCACACCTA CTACGTGTGTACCTGGGACCGCCGCCTGGCTGTGGCCATCCTGACAGCCATCAACCTGCTGGCT TACGTGGCTGACCTGGTGTAC 30 ProteinCfa.15485.1.A1_s_at 0.01 PREDICTED: Canis 100GGAGCAGTCAGAACTAAGACATGGTCCGTTTTA Kinase C familiaris similar to  CTATATGAAGGAGCCACTCACCACAGACCCTGT Binding protein kinase CTGATTTGGTACCGCAGGATGGACGGAA Protein binding protein 1isoform b; transcript variant 11 (LOC477252); mRNA

TABLE 10 Summary of enes affecting glucocorticoid receptors and nitricoxide production Gene Expression Compared Gene to Control Role Kinesin ↓Transport of organelles from the (−) to (+) ends. Binds microtubules.ATPase activity Capping Protein ↓ Part of dynactin-dynein hetero-complexCalmodulin ↓ Directly influences calcium dependent dynein activity.Binds to nitric oxide synthase and up regulates the production of nitricoxide Dynein ↓ Transport of organelles from the (+) to (−) ends. Bindsmicrotubules. ATPase activity and force production Dynactin ↓Cytoplasmic dynein activator. Binds mirotubules and ↑ average length ofdyein movements. Heat Shock Protein 1 ↓ Necessary for beta (HSP90)glucocorticoid receptor binding and fast transport of dynein complex tonucleus. Calcinuerin activity. Enhances the nitric oxide production bybinding to nitric oxide synthase PPlase ↓ Necessary fordynein/glucocorticoid interaction and movement Calcinuerin ↓ Part ofdynactin-dynein hetero-complex. Catalyzes the conversion of arginine tocitrulline and nitric oxide Protein kinase C ↓ Calcium-activated,phospholipid- dependent, serine- and threonine- specific enzyme. ProteinKinase C ↓ Associated with protein Binding Protein kinase CEffect of Nutrition on Genes Involved with DNA Damage/Protection andNeural Function

Eleven genes are identified that are related to DNA damage/protectionand neural function. With regard to the latter, the genes identified areimportant for rebound potentiation; they are believed to have apotential role in motor learning. Interestingly, of these genes, allwere down regulated except for of gamma-aminobutyric acid (GABA) Areceptor, gamma 2 which was up regulated. The compositions disclosedherein may be part of a therapeutic regimen to treat animals sufferingfrom diseases or disorders associated with or relating to DNAdamage/protection and neural function. The identity of these genes andtheir putative role in DNA damage/protection and neural function aredescribed in Tables 11 and 12 below.

TABLE 11 Genes involved in DNA damage/protection and neural function% match of probe Sequence sequence to ID No. Gene Probe P-valueBest current BLAST annotation BLAST hit Probe Target Sequence 31 Gamma-CfaAffx.26362.1.S1_at <0.01 Homo sapiens gamma-aminobutyric acid 100CCTCTTCTTCGGATGTTTTCCTTC aminobutyric acid(GABA)A receptor; gamma 2(GABRG2); AAGGCCCCTACCATTGAT (GABA)Atranscript variant 1; mRNA receptor, gamma 2 22 CalmodulinCfa.4168.1.S1_at <0.01 PREDICTED: Canis familiaris similar to 52.54237CCACCCATGGTGACGATGACACA calmodulin 1; transcript variant 3CATCCTGGTGGCATGCGTGTGTTG (LOC480416); mRNAW GTTTAGCGTTGTCTGCGTTGTACTAGAGCGAAAATGGGTGTCAGGCTTG TCACCATTCACACAGAAATTTAAAAAAAAAAAAAAAANNNNGANAAAAAA CCTTTACCAAGGGAGCATCTTTGGACTCTCTGTTTTTAAAACCTCCTGAA CCATGACTTGGAGCCAGCAGATTAGGCTGTGGCTGTGGACTTCAGCAC AACCATCAACATTGCTGATCAAGAAATTACAATATACGTCCATTCCAAGT T 28 Calcinuerin Cfa.19761.1.S1_at <0.001PREDICTED: Canis familiaris similar to 98.83382 GAATTAACAATCTGCTTGAGCCCCprotein phosphatase 3 (formerly 2B); AAAACACTACTTATGCACTTCACTTcatalytic subunit; beta isoform  GCCAAAAGATTTGNGCAAGGTTTTG(calcineurin A TACCCTGGTAAATGATGCCAAAGTTbeta); transcript variant 5 (LOC479248); TGTTTTCTGTGGTGTTTGTCAAATG mRNATTCTATGTATAATTGACTGTCTGTAA CATGCTGTTTNCTTCCTCTGCAGATGTAGCTGCTTTCCTAAATCTGTCTG TCTTTCTTTAGGTTAGCTGTATGTCTGTAAAAGTATGTTAAATTAAATTAC TCTATCAGACGCTTGTCTGTCTTTTGATGTAGAAGCAACTTTGTAGCACC TTGTTTTGAGGTNNGCTGCATTTGT TGCTGTACTTTGTGCAT 32Calcium/calmodulin- Cfa.3884.1.S1_at <0.01Homo sapiens PTEN induced putative 24.10714 GGTGCTGTTCACCACAGTAAGTGdependent kinase 1 (PINK1); mRNA GCCTCTCAGTGTTGCTGACCAAAGprotein kinase II TGTGAAATCCTAGAGCTTCAGGGG AGAGGACGTGGGGGAAATCCGGGGCTTGACTTTATAATAGGATTATAG AGATGAAAAGTACACCTTGCTTTAGGCAACAGTTGGGATTCCTAAGACG CATGTGTAAGAGCATATGTGAAATCCCTTCCCCATTGTTGATCTCTACTC ACAGAATTTTGTCTTTATTATGGTGTAAGAATCACTCTTAAAGCCACATAT TCAATTCAAAGCAAATACGTGTTCTGCAGTTGCAAATGTGTATTTAATTC TTCACAATTCCTGTAAG 33 AdenylateCfaAffx.5462.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to 100GAAACTCGGTCTGGTGTTCGATG cyclase-Adenylyl cyclase-associated protein 1 (CAP ACGTCGTGGGCATTGTGGAGATAAassociated 1); transcript variant 1 (LOC475317); mRNATCAATAGTAGGGATGTCAAAGTTCA protein 1 GGTAATGGGTAAAGTGCCAACCATTTCCATCAACAAAACAGATGGCTGC CATGTTTACCTGAGCAACAATTCCCTGGATTGCGAAATAGTCAGTGCCA AATCTTCTGAGATGAATGTCCTCATTCCTACTGAAGGCGGTGACTATAAT GAATTCCCAGTCCCTGAGCAGTTCAAGACCCTATGGAATGGGCAGAAG TTGGTCACCACAGTGACAGAAATTGCTGGATAAGCGAAGTGCCACTGGG TTCTTTGCCCTCCCCCTCACACCATGGGATAAATCTATCAGGACGGTTCT TTTCTACATTTCCTTTACCTTTCTGC TCTTAAACTGCTT 34Protein Cfa.6174.1.A1_at <0.01 PREDICTED: Canis familiaris similar to100 AAATCTTACGAAGCCCAATATGCA Phosphatase Iprotein phosphatase 1A isoform 1;  GGGAGTTAACTGAAAACTATCTTGGtranscript variant 2 (LOC480344); mRNA CAGTGAGGTTGGCACTGTTGATAAAGCTGGTCCCTTCCTTTAACTGTCT TTTAGGTTGTTCTTGCCTTGTTGCCAGGAGTATTGCAGGTAATACAGTAT ATTCATAAGAATATCAATCTTGGGGCTAAAATGCCTTGATTCTTTGCACC TCTTTTACAAGTCCTTACGTTGAATTACTAATTGATAAGCAGCAGCTTCCT ACATATAGTAGGAGACTGCCACGTTTTTGCTATCATGATTGGCTGGGCCT GCTGCTGTTCCTAGTAAGGTAT 35 DiazepamCfaAffx.14836.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to 100AATGGTGCCATCTTACTGAGGGAT binding inhibitorperoxisomal D3; D2-enoyl-CoA isomerase TTTGTAGGCTGTTTTATAGATTTTCCisoform 1 (LOC478706); mRNA TAAGCCTCTGGTTGCAGTGATAAATGGTCCAGCCATAGGAATCTCCGTC ACCATTCTCGGGCTATTCGATCTTGTGTATGCTTCCGACAGGGCAACATT TCACACTCCTTTTACTGACCTGGGCCAAAGTCCAGAAGGATGTTCCTCGT TAACTTTTCCCAAGATAATGGGCCAAGCCAAGGCAGCAGAGATGCTCAT GTTTGGAAAGAAGTTAACAGCTAGAGAAGCCTGTGCTCAAGGACTTGTT ACTGAAGTTTTTCCCGATAGCACTTTTCAGAAAGAAGTTTGGACCAGGC TGAAAGCATATTCAAAACTCCCCCGAAATACCTTGCATATTTCCAAACAG AGCATCAGAAATCTTGAGAAAGAAAAGCTACATGCTGTTAACGCAGAAG AAAACAGCGTCCTCCAGGAAAGGTGGCTGTCAGACGAATGCATAAATG CAGTCATGAGCTTCTTATCCCGGAA GGCCAA 36Tumor protein Cfa.1611.1.A1_s_at <0.01PREDICTED: Canis familiaris similar to 97.90874 ATGATAGTTGCCATGCCAACCAGp53 binding tumor protein p53 binding protein; 1;CTCCAGAATTACCGCAATTATTTGT protein transcript variant 4 (LOC478274); mRNATGCCTGCAGGGTACAGCCTTGAGG AGCAAAGAATTCTGGATTGGCAACCCCGTGAAAACCCTTTCCACAATCT GAAGGTACTCTTGGTGTCAGACCAACAGCAGAACTTCCTGGAGCTCTG GTCTGAGATCCTCATGACGGGGGGGGCAGCCTCTGTGAAGCAGCACCA TTCAAGTGCCCATAACAAAGATATTGCTTTAGGGGTATTTGACGTGGTG GTGACGGATCCCTCATGCCCAGCCTCGGTGCTGAAGTGTGCTGAAGCA TTGCAGCTGCCTGTGGTGTCACAAGAGTGGGTGATCCAGTGCCTCATT GTTGGGGAGAGAATTGGATTCAAGCAGCATCCAAAATACAAACATGATT ATGTTTCTCACTAATACTTGGTCTTAACTGATTTTATTCCCTGCTGTTGTG GAGATTGTGNTTNNNCCAGGTTTTAAATGTGTCTTGTGTGTAACTGGATT CCTTGCATGGATCT 4 UbiquitinCfaAffx.275.1.S1_s_at <0.001 PREDICTED: Pan troglodytes LOC46194197.19626 GATTTGGCCCGTGACCCTCCAGC conjugating (LOC461941); mRNAACAATGTTCTGCAGGTCCTGTTTGG enzyme E2D 3 GATGATATGTTTCATTGGCAAGCCACAATTATAGGACCTAATGAGAGCCC ATCAAGG 5 NEDD8 ultimate Cfa.12556.1.A1_s_at<0.001 PREDICTED: Canis familiaris similar to 99.12473GGAATGGGCTACTCTACTCATGC buster-1 NEDD8 ultimate buster-1 (NY-REN-18AGNCAAGCAGGNCCTGCATCAGGC antigen)(LOC475542); mRNACAGTGGGAACCTGGACGAAGCCCT GAAGATTCTTCTCAGCAATCCTCAGATGTGGTGGTTAAATGATTCAGATC CTGAAACGANCAACCAGCAAGAAAGTCCTTCCCAGGAAAACATTGACCA ACTGGTGTACATGGGCTTCGACGCTGTGGTGGCTGATGCTGCCTTGAG AGTGTTCAGGGGAAACGTGCAGCTGGCAGCTCAGNCCCTCGCCCACAA CGGAGGAACTCTTCCTCCTGACCTGCAGCTCTTGGTGGAAGACTCTTC ATCAACGCCATCCACGTCCCCTTCCGACTCCGCAGGTACCTCTAGTGC CTCAACAGATGAAGATATGGAAACCGAAGCTGTCAATGAAATACTGGAA GATATTCCAGAACATGAAGAAGATT ATCTTGACTCAACACTGGAAG37 BCL2-associated CfaAffx.6742.1.S1_s_at <0.01Canis familiaris BCL2-associated X protein 100 GGCCCACCAGCTCTGAGCAGATCX protein (BAX) (BAX); mRNA ATGAAGACAGGGGCCCTTTTGCTTCAGGGTTTCATCCAAGATCGAGCA GGGCGAATGGGGGGAGAGACACCTGAGCTGCCCTTGGAGCAGGTGCC CCAGGATGCATCCACCAAGAAGCTGAGCGAATGTCTCAAGCGCATCGG AGATGAACTGGACAGTAACATGGAGTTGCAGAGGATGATCGCAGCTGT GGACACAGACTCTCCCCGTGAGGTCTTCTTCCGAGTGGCAGCTGAGAT GTTTTCTGATGGCAACTTCAACTGGGGCCGGGTTGTTGCCCTCTTCTAC TTTGCCAGCAAACTGGTGCTCA

TABLE 12 Summary of genes important for rebound potentiation and DNAintegrity Gene Expression Compared Gene to Control RoleGamma-aminobutyric ↑ Involved in single channel acid (GABA) A receptor,conductance (Cl- channel) gamma 2 Calmodulin ↓ Influx of calcium resultsin calcium/calmodulin complex which activates CaMKII and calcineurinCalcinuerin ↓ Involved in the pathway for RP suppressionCalcium/calmodulin- ↓ Involved in induction and dependent protein kinaseII suppression of RP Adenylate cyclase- ↓ Adenlyl cyclase is involvedassociated protein 1 in suppression of RP Protein Phosphatase I ↓Dephosphorylates components in stress- activated pathways. Active PP-1results in CaMKII inhibition and RP suppression Diazepam binding ↓Displaces benzodiazepine inhibitor Down regulates the effects of GABATumor protein p53 ↓ Keep the cell from binding protein progressingthrough the cell cycle if there is damage to DNA present. Ubiquitinconjugating ↓ The regulated proteolysis of proteins by enzyme E2D 3proteasomes removes (and NEDD8 ultimate denatured, damaged buster-1) orimproperly translated proteins from cells and regulates the level ofproteins like cyclins or some transcription factors BCL2-associated ↓Accelerates programmed X protein cell death by binding to, andantagonizing the apoptosis repressor BCL2Effect of Nutrition on Genes Involved with Glucose Metabolism

Twenty four genes associated with glucose metabolism are down regulatedin animals fed the super senior diet which would suggest that theseanimals are utilizing fat (fat oxidation) instead of glucose as a fuelsource. The compositions disclosed herein may be part of a therapeuticregime in diabetic animals and/or for obesity prevention or treatment inan animal. These down regulated genes are identified and their putativerole in glucose metabolism described in detail below in Tables 13 and14.

TABLE 13  Genes involved in Glucose Metabolism % match of probe Sequencesequence to ID No. Gene Probe P-Value Best Current BLAST annotationBLAST hit Probe Target Seq. 38 Phosphorylase Cfa.10856.1.S1_at <0.01PREDICTED: Canis familiaris similar to  99.3392 GAAAGTTCACCACTGCATGTTTTAkinase phosphorylase kinase beta; transcript variantTGATCAGATAACTCATTGAAATGA 2 (LOC478139); mRNA GTCTTTGCTCTTTAGACTAAATTCCCACCTAGTACTGCCATTAAAATG AATTTGCCAGCTGGTGTGCATACTGGAAATGAAAAGATACTGAAAGAA TGGAACGAATGGTGAGCTTAACT CAGTGGCACTGTCATACTGGAAAAATACAGTAAAATCATAAAAACAG ATCTGCCAGCTGATGTTTTTATTCTCAGAAACAGCATTGTTGATAATA TTTTAGTATACAGAGCTACTGTACAATTTTTACCTTGNAAACATGACT GTGGTTTTGTATTTGTGTTGACTTTAGGGGTTGGGATAAAATNCAGT ATAATATATACCTTATCAAACNTTTTCTTTGAGCTCTTACTAAAAATAT GGCATGCATAAGATTGTTCAGAAGAGTAGACTGTTAACCTAGTTTGTA 39 Phosphorylase Cfa.10412.1.A1_s_at <0.01PREDICTED: Canis familiaris 99.36306 CTTCCAGAGCTGAAGCTGGCCATphosphorylase; glycogen; liver; transcript TGATCNAAATTGACAATGGCTTCTvariant 1 (PYGL); mRNA TCTCTCCCAAGCAGCCTGNCCTC TTCAAAGATTTAATCAATATGCTATTTTATCATGACAGGTTTAAAGTCT TCGCAGACTATGAAGCCTATGTCAAGTGTCAAGAAAAAGTCAGCCAG CTGTACATGAATCCAAAGGCCTG GAACACAATGGTACTCAAAAACATAGCTGCCGCAGGGAAGTTCTCTA GTGACCGAACAATTAAGGAATATG CCAGGGACATCTGGAACATGGAACCTTCAGATCTCAAGATTTCCCTA TCCAATG 40 Glycogen Cfa.913.1.A1_s_at <0.01PREDICTED: Canis familiaris similar to 99.49622 GACTCCACCGGAGGCAATTGCACsynthase kinase Glycogen synthase kinase-3 beta (GSK-3TGTGTAGCCGTCTGCTGGAGTAT 3 beta); transcript variant 1 (LOC478575);ACACCAACTGCCCGATTGACACC mRNA ACTGGAAGCTTGTGCACATTCATTTTTTGATGAATTAAGGGACCCAAA TGTCAAACTACCAAATGGGCGAGACACACCTGCACTCTTCAACTTCA CCACTCAAGAACTGTCAAGTAATCCACCTCTAGCTACCATCCTTATTC CTCCTCATGCTCGGATTCAAGCAGCTGCTTCAACCCCTACAAATGCC ACAGCAGCCTCAGATGCTAATGC CGGAGACCGTGGACAGACGAACAATGCCNCTTCTGCATCAGCTTCTA ACTCCACCTGAACAGTCCCGAGC AGCCAGCTGCACAGGAAGAACCACCAGTTACTTGAGTGTCACTCA 22 Calmodulin Cfa.4168.1.S1_at <0.01PREDICTED: Canis familiaris similar to 52.54237 CCACCCATGGTGACGATGACACAcalmodulin 1; transcript variant 3 CATCCTGGTGGCATGCGTGTGTT(LOC480416); mRNA GGTTTAGCGTTGTCTGCGTTGTAC TAGAGCGAAAATGGGTGTCAGGCTTGTCACCATTCACACAGAAATTT AAAAAAAAAAAAAAAANNNNGANAAAAAACCTTTACCAAGGGAGCATC TTTGGACTCTCTGTTTTTAAAACCTCCTGAACCATGACTTGGAGCCAG CAGATTAGGCTGTGGCTGTGGAC TTCAGCACAACCATCAACATTGCTGATCAAGAAATTACAATATACGTC CATTCCAAGTT 29 Protein Kinase CCfaAffx.408.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to99.64664 TTCAGTTCCTGTCTCATGGCCGCTmyeloid-associated differentiation marker CCCGGGACCATGCCATCGCCGCC(LOC611521); mRNA ACTGCCTTCTCCTGCATCGCTTGT GTGGCTTATGCCACCGAAGTGGCCTGGACCCGGGGCCGTCCGGGA GAGATCACCGGCTACATGGCCAN TGTGCCCGGCCTGCTCAAGGTGCTGGAGACCTTTGTGGCCTGCATC ATCTTCGCCTTCATCAGCAACCCC TCCCTGTACCAGCACCAGCCGGCCCTGGAGTGGTGTGTGGCCGTCT ACTCCATCTGTTTCATCCTGGCGG CTGTGGCCATCCTAGTGAACCTGGGGGACTGCACCAACATGCTGCC CATCTCCTTCCCCAGTTTCCTGTC GGGCCTGGCCCTGCTCTCCGTCCTGCTGTATGCCACGGCTCTGGNT CTCTGGCCGCTCTACCAGTTCAA CGAGAAGTATGGTGGCCAGCCCCGTCGGTCGAGGGATGTTAGCTGC GCCGACAGGCACACCTACTACGT GTGTACCTGGGACCGCCGCCTGGCTGTGGCCATCCTGACAGCCATC AACCTGCTGGCTTACGTGGCTGA CCTGGTGTAC 30Protein Kinase C Cfa.15485.1.A1_s_at <0.01PREDICTED: Canis familiaris similar to 100 GGAGCAGTCAGAACTAAGACATGBinding Protein protein kinase C binding protein 1 isoform b;GTCCGTTTTACTATATGAAGCAGC transcript variant 11 (LOC477252); mRNACACTCACCACAGACCCTGTTGAT GTTGTACCGCAGGATGGACGGAA 41 Hexokinase 3Cfa.19125.2.S1_at <0.01 Macaca fascicularis testis cDNA; clone; 76.70683TAATGACTGCCAACTCACTGTTTG QtsA-14856; similar to human receptorTTGGAGTTATATGCAGAAATAAAG associated protein 80 (RAP80); mRNA;NCCAAGTCTTCAGAAACAGGCTTC RefSeq: NM_016290.3 AGGATGCCCTCACCAGGGATGGAAGAGGCAGGCTGCAGCAAAGAGA TGCAGAGTTCCCTTGCACATCTCGACTTAAATGAGTCTCCCATCAAGT CTTTTGTTTCCATTTCAGAAGCCACAGATTGCTTAGTGGACTTTAAAA AGCAACTTAACGTTCGGCAAGGT AGTCGGACACGGACCAAAGCAGGCAGAGGAAGAAGGAGAAAACCCT GAATTTCTAGGGTCCAGACACCC GACAAAACCATTAGCAATAGGGGTGGGCCGTGTCATTAAGTGTTAGT GGCTTCTGTTTCATTGTTGAACAAGTTTTTTGGCCCNGCAGTTTTCAC CACCAGCACCAACTCAGCATTCTTGTTTTGATGTTTTCTATAAGCTATA CAGACAATTGTGTATAGTATTCTGTTTTATAACAGTCTGGATTCACTT 42 Fructose 1,6 CfaAffx.26135.1.S1_s_at <0.01PREDICTED: Canis familiaris aldolase A, 100 AGTGGCGCTGTGTGCTGAAAATTbisphosphatase transcript variant 1 (LOC479787); mRNAGGGGAACACACTCCCTCAGCCCT TGCGATCATGGAAAATGCCAACG TTCTGGCCCGTTAT 43Glyceraldehyde AFFX-Cf_Gapdh_3_at <0.01Canis familiaris glyceraldehyde-3-phosphate 100 AGCTCACTGGCATGGCCTTCCGT3-phosphate dehydrogenase (GAPDH); mRNA GTCCCCACCCCCAATGTATCAGTTdehydrogenase GTGGATCTGACCTGCCGCCTGGA GAAAGCTGCCAAATATGACGACATCAAGAAGGTAGTGAAGCAGGCAT CGGAGGGACCCCTCAAAGGCATC CTGGGCTACACTGAGGACCAGGTGGTCTCCTGTGACTTCAACAGTGA CACCCACTCTTCCACCTTCGACG CCGGGGCTGGCATTGCCCTCAATGACCACTTTGTCAAGCTCATTTCC TGGTATGACAATGAATTTGGCTACAGCAACCGGGTGGTGGACCTCAT GGTCTACATGG 44 Glucose 6- Cfa.19351.1.S1_at<0.01 Homo sapiens cDNA FLJ30869 fis; clone 15.11194GAATGTGTTGGGAGACTGAGGCC phosphate FEBRA2004224 CCCCATGTTTTTAATGCGCACTGGdehydrogenase GGACAACCATCTAAGGTCTAGAAA CTTTTGGACCATAGGAAAGATAGGTTTATGGTCCTCTTCCAGATGCAG CCCTAGGAGAGCATTCCCATGGGGTCTCTGGATCCCTTTCNTTGCTC TGTGAGGCTCTGTGACCACCTTTT GNNNTGNNGGGGGCAGGGGGNCTTCCTCAGCTCCGCCTCCAGTGC CCCCAGGTCCCCCACGGCTCACA GTCCNTGAAAATTCAGAGCTGCCCTGTAAGGATTTTGTCCACTGGGC AATTCAGATATACTTCGATATCCCTGAGAAAGAAGAGGCAGCAGCAA ACACTCCCNAGGGCATCTGTCTC AGNANTCTCTCNTTGNATGAGACAGAAGCCTACTTTTCAGAAANCTTA TCANGGNTACTTTATAAGAAACTTTTTTTTTTTTNCTAAAATCAGACAA AAGGTGGCTTNTGCATATTCTTNATTAATAACTGTGTCTTTGTCTCCT CTGCTTAACTTTAGGA 45 EnolaseCfaAffx.30133.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to97.72257 GGTACATCACGCCTGATCAGCTG T21B10.2b; transcript variant 1GCTGACCTCTACAAGTCCTTCATC (LOC479597); mRNA AGGGACTACCCAGTGGTGTCTATCGAAGACCCCTTCGACCAGGATG ACTGGGAAGCTTGGCAGAAATTC ACTGCCAGCGCTGGAATCCAGGTGGNGGGGGANGATCTCACCGTGA CCAACCCAAAGCGGATTTCCAAG GCTGTGGGCGAGAAATNGTGCAACTGCCTCCTGCTTAAGTGAACCA GATTGGCTCTGTGACCGAGTCTC TTCAGGCGTGCAAGCTGGCCCAGTCCAATGGGTGGGGCGTCATGGT GTCGCATCGCTCCGGGGAGACCG AAGATACCTTCATCGCTGACCTGGTGGTGGGANTCTGCACTGGGCAG ATCAAGACGGGTGCACCATGCAG ATCTGAGCGCTTGGCCAAGTACAACCAGATCCTCAGAATTGAAGAG GAACTGGGTAGCAAGGCCAAGTT CGCCGGCAGAAGCTTCAGAA 46Lactate Cfa.300.1.S1_at <0.01 PREDICTED: Canis familiaris similar to L-97.99427 ATCTGACCTGTTACTCAAGTCGTA dehydrogenaselactate dehydrogenase A chain (LDH-A) ATATTAAAATGGCCTAAGAAAAAA(LDH muscle subunit)(LDH-M)(Proliferation- ACATCAGTTTCCTAAAGTTACACAinducing gene 19 protein); transcript variant TAGGAATGGTTCACAAAACGCTGC1 (LOC476682); mRNA AGCTATGTCCTGATGCTGGATGA GACCTGTCTTGTGTAGTCCTAAATTGGTTAACGTAATATCGGAGGCA CCACTGCCAATGTCATATATGCTGCAGCTACTCCTTAAACCAGATGTG TATTTACTGTGTTTTGTAACTTCTGATTCCTTCATCCCAACATCCAACA TGCCTAGGCCATCTTTTCTTCTTCAGTCACATCCTGGGATCCAATGTA TAAATTCAATATTGCATGTATTGTG CATAACTCTTCTA 47Citrate lyase Cfa.10361.2.S1_at <0.01PREDICTED: Canis familiaris similar to 98.49624 AGTATGCCAGATCGGAACCTTTTTcitrate lyase beta like (LOC476974); mRNA CCCATTTACAGTTCATGTTAATCCAATTTTTTTTATTATCTCACTGGCC AGTTATTCCTTTAAAAATGAACTTCCTTCTTTTTGATTCCAAGCTTATGA TTTTACTGCTCATTAATGTGTTACAAATATGCACTTAATGATTTCACAG GGAGATAAAATAGTGAAGAGAGA TGGGCTGAGGGGCTGTTAGGACTTTAATGAAACAGATCTTTCCCGAA TATTTCTCCCTTCACATTTCTCACATTAGATGTTTCCCACATTGTTCTA CTCCACACTATAAATAATTTTAAGGCCAATCTTAAAAAATGGTAGTTA AGTGAAGGGGTTGTGTTTATTTCACTAGAAATCTGATAAAACGAGAGA TGACATAGAAAAAGTTATCATTTTTGTTCATACAGATGGCTTCTAAAAA TAAATCTTCAAAACTGATTACTTTTAACCTCCACCTCCCAAAATGAAAC ATCCCTACATTTGAACTGCTAGGTGATAACTCTGAAAGCCCTCATCC 48 Glycerol kinase CfaAffx.21204.1.S1_s_at <0.01PREDICTED: Canis familiaris similar to 100 GGGTACATCCTATGGCTGCTATTTglycerol kinase isoform 2; transcript  CGTCCCCGCGTTTTCAGGGTTATAvariant 8 (LOC480872); mRNA TGCACCTTACTGGGAGCCCAGTGCAAGAGGGATCATCTGTGGGCTC ACTCAATTCACCAATAAATGCCATATTGCTTTTGCTGCATTAGAAGCT GTTTGTTTCCAAACCCGGGAGATTTTGGATGCCATGAACCGAGACTG CGGAATTCCACTCAGTCATTTGCA GGTAGATGGAGGAATGACCAACAACAAAATTCTTATGCAACTACAAG CAGACATTCTATATATCCCAGTAGTGAAGCCCTCGATGCCAGAAACA ACTGCCCTGGGAGCTGCCATGGC AGCCGGGGCTGCGGAGGGAGTTGGTGTTTGGAGTCTTGAACCCGA GGATCTGTCAGCAGTCACGATGG AGCGATTTGAACCCCAGATCAATGCTGAGGAAAGTGAAATTCGTTACT CTACATGGAAGAAGGCTGTGATG AAGTCAGTGGGCTGGGTTAGAACTCA 49 Transketolase CfaAffx.13684.1.S1_s_at <0.01Homo sapiens transketolase (Wernicke- 86.53846 GAAGATCTGGCCATGTTTCGGTCkorsakoff syndrome): mRNA (cDNA clone CATCCCCACTGCTACGATCTTTTAMGC: 15349 IMAGE: 4310396); complete cds CCCAAGTGACGGGGTGTCAACAGACAAGGCGGTGGAATTAGCAGCC AATACAAAGGGCATCTGCTTCATC CGGACCAGCCGCCCAGAAAACGCCATCATCTATAACAACAATGAGGA TTTCCAAATCAAACAAGCCAAGGTGGTCCTGAAGAGCAAGGATGACC AGGTGACTGTGATTGGGGCCGGA GTGACCCTACATGAGGCCTTGGCTGCTGCTGAACTGCTGAAGAAAG AGAAGATCAACATTCGTGTGTTGG ACCCCTTCACCATCAAGCCCCTGGACAGAAATCTCATTCTCGAAAGC GCCCGTGCGACCAAGGGCAGGAT CGTCACCGTGGAGGACCATTACTATGAAGGTGGCATAGGTGAGGCA GTGTCCTCTGCCTTGGTGGGTGA GCCTGGCATCACCGTCTCCCGCCTTGCAGTTGGTGAGGTACCAAGA AGCGGGAAGCCAGCTGAGCTGCT GAAGATGTTTGGCATTGACAGGGACGCCATCGCACAAGCTGTGAGG GACCTTGTCGCCAA 50 Ribulose Cfa.13084.1.A1_s_at<0.01 Homo sapiens SLIT-ROBO Rho GTPase 57.79468 CCCCAAGGAGATGAGGAGCGATGphosphate 3- activating protein 2(SRGAP2); mRNA ACCCCACCAACAGGAANAACAGCepimerase CCACTGAAGGGCTGGTGTGTGTG TNCTTCACGTGCCAGAAGAGAAGTTTAGATCCTCCCAGGGGAATCG CAATGTTGTGGCGTCCTGACTTGTATGTCACCTTTTGTGTAAAAATGG TATATTCTTTAAAATAGTGTTGATAACTGGAATATTGTATGTATGCTTG GAGATGCTTTGTGTGAACCTAAGACTGTCACTCAACAGATGTTGGATT GGG 51 Ribose 5- Cfa.335.2.S1_at <0.01PREDICTED: Canis familiaris similar to 100 AGCCTTTCTACTGACCCTGCAAGAphosphate ribose 5-phosphate isomerase A (ribose 5-GTGGAGCGTGTTCACCTTGAACC isomerasephosphate epimerase)(LOC475755); partial CCCAGCGTGCAGCTGAGGTAGAC mRNAATGCCTCTCCAGGAGCCTTTGCC TTAATGCATCTGTGCCAGACAGAC GGCTGG 52 Cytochrome cCfaAffx.4942.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to 100GGCAGTTTGAAAATAAAGTTCCAG oxidase cytochrome c oxidase: subunit 7a 3AGAAACAAAAGCTATTTCAGGAGG polypeptide VIIa- (LOC611134); mRNAATAATGGAATTCCAGTGCATCTAA liver/heart, AGGGTGGAGTAGCTGATGCCCTCmitochondrial CTGTATAGAGCCACTATGATGCTT precursor ACAGTTGGTGGAACAGCATATGCCATGTATCAGCTAGCTGTGGCTTC TTTTCCCAAGAAGCA 53 Cytochrome cCfa.15065.1.S1_at <0.01 PREDICTED: Canis familiaris similar to 99.75961GGTCCGCAGTCGTTCTGTGCGGT oxidase subunitCytochrome c oxidase polypeptide VIII-liver; CATGTCTGTGCTGGTGCCGCAGCVIII liver form mitochondrial precursor (Cytochrome cTGCTGAGGGGCCTAACAGGCCTC oxidase subunit 8-2)(LOC476040); mRNAACCCGGCGGCTCCCGGTGCATCG TGCCCAGATCCATTCCAAGCCGC CGCGGGAGCAGCTCGGGACCATGGATGTTGCCGTTGGGCTCACCT NCTGCTTCCTGTGTTTCCTCCTGC CATCGGGCTGGGTCCTGTCACACCTGGAGAGCTACAAGAAGCGGGA GTGAAGGGGGCTGTCCTGTCCCT CACCCTGTGACCTGACCACCCCTGGCCTGTCCTGATCATGTCTGCT GCATTCCTGGCCGGCCTTCCATG GATCATGTCCTTCAATTACAGTGACCTCTTCTACAGTCATGACCTCTT GATTTCTCCATGGTGACATCCTGG GACCAAACATATTGGTTTATAA54 Ubiquinolucytochrome Cfa.1425.2.A1_at <0.01PREDICTED: Canis familiaris similar to 27.18053 CTTATGCATTCCTTCCAAAATTGGc reductace Ubiquinol-cytochrome-c reductase complexATCATTTAGGTCAAATTATTTGATG core protein 2; mitochondrial precursorTTAAATCATAAGTTTTCATTTGCTT (Complex III subunit II); transcript ACATTTACGATATCAGCGTCAGCT variant 1 (LOC479815); mRNAACGGAATCAATCTGCTGAAGGAC CGTGGCTGGCGGCGTGTACGATC GAGCAACCAGCGCCTGGGACCCGACTTCATCCAGGAACCCCTCAGAA GACTCCACTGACATTAGGAAGACTCATAAGAACCTTACAAGAAAAAGT ATCAACCCCATCAAAACGGCAGAAAAGAAACATATCTTGTTATTAGTA GCTGAAATTCCATTTTCTACATGTTGCCATACCTTATAAAAACTACAC TAAGCTACGCTTAAGGAAATACATTTTCTTAAATAAATTAGAATTGAAA CCAATTTTTAAGTAAATCTAGGGNTTCAATTTATTCTCATTGNGTNTTG TTTCTGGTGCAATCATGAANAACAGCATNCTATTAACCAACCTTGGTC CCATGTACATAA 55 ATP synthaseCfaAffx.3186.1.S1_s_at <0.01 PREDICTED: Canis familiaris similar to ATP96.57651 AATTGGGACTGTGTTTGGGAGCC synthase; H+transporting; mitochondrial F0 TCATCATTGGTTATNCCAGGAATCcomplex; subunit c isoform 2a precursor CCTCTCTGAAGCAACAGCTCTTCT(LOC477595); mRNA CCTACGCCATTCTGGGCTTTGGC CTCNCGGAGGCCATGGGGCTTTTTTGCCTGATNGTGGCCTTTCTCAT CCTGTTNGCCATGTGAAGGAGTCGTCTCCACCTCCCATAGGTCTTTC TCCCATGTCTTGTCTGCCCTGTATGCCCTGTATGTTCCTTTTCCTATA CCTCCCCAGGCAGCCTGGGGAAA GTGGTTGGCTCAGGGTTTGACA56 NADH- Cfa.4415.1.S1_at <0.01 PREDICTED: Canis familiaris similar to98.20789 GGTGACTTTGGACGTCCGTTCCT ubiquinoneNADH-ubiquinone oxidoreductase MLRQ GCTCTGTGGAGGCNNTGCTTCGToxidoreductase subunit (Complex I-MLRQ)(CI-MLRQ) TCCGGGCCTTGCGGCAACTCGGT(LOC477682); mRNA NTTTCCTTCCCCTGCGCGGGAGA CCTCTGCCACAACCATGTTACGCCAGATCATCGGTCAGGCCAAGAA GCATCCGAGCTTGATCCCCCTCTT CATATTTATTGGGGCAGGAGGTACTGGAGCAGCGCTGTATGTATTG CGCTTGGCATTGTTCAATCCAGATGTTAGTTGGGATAGGAAGAATAAC CCAGAACCTTGGAACAAACTGGGTCCCAATGATCAATACAAGTTCTA CTCAGTGAATGTAGATTACAGCAAACTGAAGAAAGAAGGTCCAGACT TCTAAATGAAATGTTTCACTATAAAGCTGCTTAGAATGAAGGTCTTCCA GAAGCCATCCGCACAATTTTCCACTTATCCAGGAAATATTTCCCCTCT AAATGCACGAAATCATGTTTGGTGTATTGTGTTGGGGTTTACACTNNAN NANTAAATATCTGAAACTTGANANGTGTCACTATTTAATGCTGAAAAT TTGCTCTGAACTTTA 57 Facilitated Cfa.1370.1.A1_at<0.01 Homo sapiens cDNA FLJ44038 fis; clone 23.95833TTGGAAGGATGGATGCTTGCCCC glucose TEST14028880; highly similar to GlucoseAGGTCATGGACACCTCCACAAAT transporter/ transporter type 3; brainCATCTAGTTTCCCAGTATTTTTATA Glucose AATGGAGATTGGGCTCCATGACAtransporter-like CTTTACTTGGTCTTCCTTCTTACAT protein IIIAGGTTTTTTGATTACCCTTTCTCTC (GLUT3) CTTGGTGCTTATATACTTAAGACCCTTTAGCCAAACCCTTGCCAATGA CAGTATTTCAGTCACTAGTTCTCACTGTTTCCTCTGATCATTGAGCCT TTGGAAAAAAAATCTCACAGAGCTTATATGTAATGGGGCTTGGTTGAA CAGATGACTTCCTGTAACTGCACCTCTACTTTTGGCTTCTCAAAAACA GTGGGTTGGCAGTAATGCAGCGTGGAAGTTTTCCCATTTCTCAGTGA C

TABLE 14 Summary of Genes involved in Glucose Metabolism Gene ExpressionCompared to Gene Control Role Phosphorylase kinase ↓ Necessary foractivation of glycogen synthase which stores glucose as glycogenPhosphorylase ↓ Necessary for glycogen conversion to glucose 1-phosphate which feeds into glycolysis Glycogen synthase ↓ Necessary foractivation of kinase 3 glycogen synthase which stores glucose asglycogen Calmodulin ↓ Necessary for activation of glycogen synthasewhich stores glucose as glycogen Protein Kinase C ↓ Necessary foractivation of glycogen synthase which stores glucose as glycogen ProteinKinase C Binding ↓ Necessary for activation of Protein glycogen synthasewhich stores glucose as glycogen Hexokinase 3 ↓ Necessary for glucoseconversion to pyruvate to enter the TCA cycle Fructose ↓ Necessary forglucose 1,6 bisphosphatase conversion to pyruvate to enter the TCA cycleGlyceraldehyde 3- ↓ Necessary for glucose phosphate dehydrogenaseconversion to pyruvate to enter the TCA cycle Glucose 6-phosphate ↓Involved in pentose dehydrogenase phosphate pathw ay Enolase ↓ Necessaryfor glucose conversion to pyruvate to enter the TCA cycle Lactatedehydrogenase ↓ Involved in converting private to lactate Citrate lyase↓ Necessary for citrate conversion to oxaloacetate which feedsacetyl-CoA into the fatty acid synthesis pathway Glycerol kinase ↓Necessary for changing glycerol into DHAP which feeds into glycolysisTransketolase ↓ Involved in pentose phosphate pathway Ribulose phosphate3- ↓ Involved in pentose epimerase phosphate pathway Ribose 5-phosphate↓ Involved in pentose isomerase phosphate pathway Cytochrome c oxidase ↓Associated with the polypeptide VIIa- production of ATP (energyliver/heart, mitochondrial source) in the electron precursor transportchain which is associated with the TCA cycle Cytochrome c oxidase ↓Associated with the subunit VIII liver form production of ATP (energysource) in the electron transport chain which is associated with the TCAcycle Ubiquinol--cytochrome c ↓ Associated with the reductase productionof ATP (energy source) in the electron transport chain which isassociated with the TCA cycle ATP synthase ↓ Associated with theproduction of ATP (energy source) in the electron transport chain whichis associated with the TCA cycle NADH-ubiquinone ↓ Associated with theoxidoreductase production of ATP (energy source) in the electrontransport chain which is associated with the TCA cycle Facilitatedglucose ↓ Involved in glucose uptake transporter/Glucosetransporter-like protein- III (GLUT3)

What is claimed is:
 1. A kit for detecting mRNA levels and/or proteinlevels of a gene having a sequence of any one or more of SEQ ID NOs:1-57 in a biological sample, said kit comprising: (a) a polynucleotideof said gene or a fragment thereof; (b) a nucleotide sequencecomplementary to that of (a); (c) a polypeptide encoded by said gene, ora fragment thereof; or (d) an antibody to a polypeptide encoded by saidgene, or a fragment thereof wherein components (a), (b), (c) or (d) maycomprise a substantial component.